From a89f8b309622d2edbf4490ad60b8c0e5b771dddb Mon Sep 17 00:00:00 2001 From: Peter Robinson Date: Sun, 7 Jan 2024 08:38:15 +0100 Subject: [PATCH] LMNA --- data/LMNA/Bar_2017_27920058-DB386_10m.json | 210 -------- data/LMNA/Bar_2017_27920058-DB392.json | 118 ----- data/LMNA/Bar_2017_27920058-DB423.json | 158 ------ notebooks/LMNA/Bonne_LMNA_2000.ipynb | 563 ++++++++++++++++++++- notebooks/LMNA/Brodsky2000_LMNA.ipynb | 19 - notebooks/LMNA/input/Bonne2000.tsv | 83 +-- 6 files changed, 598 insertions(+), 553 deletions(-) delete mode 100644 data/LMNA/Bar_2017_27920058-DB386_10m.json delete mode 100644 data/LMNA/Bar_2017_27920058-DB392.json delete mode 100644 data/LMNA/Bar_2017_27920058-DB423.json diff --git a/data/LMNA/Bar_2017_27920058-DB386_10m.json b/data/LMNA/Bar_2017_27920058-DB386_10m.json deleted file mode 100644 index 77eba6aa1..000000000 --- a/data/LMNA/Bar_2017_27920058-DB386_10m.json +++ /dev/null @@ -1,210 +0,0 @@ -{ - "id" : "Bar_2017_27920058-DB386_10m", - "studyMetadata" : { - "freeText" : "The DNA sequence reads revealed roughly 50% normal LMNA sequence, but 4.7% c.1968+2T>C mutation and 41.3% c.1968+2T>A mutation.", - "createdBy" : { - "curatorId" : "HPO:ielis", - "softwareVersion" : "2.0.0-RC3-SNAPSHOT", - "timestamp" : "2023-03-20T19:18:35.056175814Z" - }, - "modifiedBy" : [ ] - }, - "publication" : { - "authors" : "Bar DZ, Arlt MF, Brazier JF, Norris WE, Campbell SE, Chines P, Larrieu D, Jackson SP, Collins FS, Glover TW, Gordon LB", - "title" : "A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.", - "journal" : "J Med Genet", - "year" : 2017, - "volume" : "54(3)", - "pages" : "212-216", - "pmid" : "27920058" - }, - "variants" : [ { - "variantType" : "SNV", - "genomicAssemblyAccession" : "GRCh38.p13", - "contigGenBankAccession" : "CM000663.2", - "strand" : "+", - "start" : 156138758, - "end" : 156138759, - "changeLength" : 0, - "id" : "nonclassic-HGPS-mild", - "md5Hex" : "a0b9ec70522aa63dd5d066d1326c8e8b", - "ref" : "T", - "alt" : "C", - "validationContext" : "VariantMetadataDefault", - "validationMetadata" : { - "variantMetadataContext" : "UNKNOWN", - "snippet" : null, - "variantClass" : "N/A", - "pathomechanism" : "N/A", - "cosegregation" : false, - "comparability" : false - } - }, { - "variantType" : "SNV", - "genomicAssemblyAccession" : "GRCh38.p13", - "contigGenBankAccession" : "CM000663.2", - "strand" : "+", - "start" : 156138758, - "end" : 156138759, - "changeLength" : 0, - "id" : "nonclassic-HGPS-severe", - "md5Hex" : "9091726c38c3cb63e5e197e66df093e2", - "ref" : "T", - "alt" : "A", - "validationContext" : "VariantMetadataDefault", - "validationMetadata" : { - "variantMetadataContext" : "UNKNOWN", - "snippet" : null, - "variantClass" : "N/A", - "pathomechanism" : "N/A", - "cosegregation" : false, - "comparability" : false - } - } ], - "individual" : { - "id" : "DB386", - "age" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "vitalStatus" : { - "status" : "ALIVE", - "timeOfDeath" : null - }, - "diseases" : [ { - "diseaseIdentifier" : { - "diseaseId" : "OMIM:176670", - "diseaseName" : "HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS" - }, - "isExcluded" : false - } ], - "genotypes" : [ { - "variantMd5Hex" : "a0b9ec70522aa63dd5d066d1326c8e8b", - "genotype" : "HETEROZYGOUS" - }, { - "variantMd5Hex" : "9091726c38c3cb63e5e197e66df093e2", - "genotype" : "HETEROZYGOUS" - } ], - "phenotypicFeatures" : [ { - "termId" : "HP:0001043", - "label" : "Prominent scalp veins", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0009125", - "label" : "Lipodystrophy", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0004322", - "label" : "Short stature", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0001596", - "label" : "Alopecia", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0007418", - "label" : "Alopecia totalis", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0034392", - "label" : "Joint contracture", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0004325", - "label" : "Decreased body weight", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 10, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0004322", - "label" : "Short stature", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : 1, - "months" : null, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0030972", - "label" : "Abnormal systemic blood pressure", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0000855", - "label" : "Insulin resistance", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0003115", - "label" : "Abnormal EKG", - "isExcluded" : true, - "onset" : null, - "resolution" : null - } ], - "sex" : "FEMALE" - } -} \ No newline at end of file diff --git a/data/LMNA/Bar_2017_27920058-DB392.json b/data/LMNA/Bar_2017_27920058-DB392.json deleted file mode 100644 index 4f2fba2e5..000000000 --- a/data/LMNA/Bar_2017_27920058-DB392.json +++ /dev/null @@ -1,118 +0,0 @@ -{ - "id" : "Bar_2017_27920058-DB392", - "studyMetadata" : { - "freeText" : "", - "createdBy" : { - "curatorId" : "HPO:ielis", - "softwareVersion" : "2.0.0-RC3-SNAPSHOT", - "timestamp" : "2023-03-20T19:18:35.056175814Z" - }, - "modifiedBy" : [ { - "curatorId" : "HPO:ielis", - "softwareVersion" : "2.0.0-RC3-SNAPSHOT", - "timestamp" : "2023-03-20T19:43:33.547310763Z" - } ] - }, - "publication" : { - "authors" : "Bar DZ, Arlt MF, Brazier JF, Norris WE, Campbell SE, Chines P, Larrieu D, Jackson SP, Collins FS, Glover TW, Gordon LB", - "title" : "A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.", - "journal" : "J Med Genet", - "year" : 2017, - "volume" : "54(3)", - "pages" : "212-216", - "pmid" : "27920058" - }, - "variants" : [ { - "variantType" : "SNV", - "genomicAssemblyAccession" : "GRCh38.p13", - "contigGenBankAccession" : "CM000663.2", - "strand" : "+", - "start" : 156138758, - "end" : 156138759, - "changeLength" : 0, - "id" : "nonclassic-HGPS-mild", - "md5Hex" : "a0b9ec70522aa63dd5d066d1326c8e8b", - "ref" : "T", - "alt" : "C", - "validationContext" : "VariantMetadataDefault", - "validationMetadata" : { - "variantMetadataContext" : "UNKNOWN", - "snippet" : null, - "variantClass" : "N/A", - "pathomechanism" : "N/A", - "cosegregation" : false, - "comparability" : false - } - } ], - "individual" : { - "id" : "DB392", - "age" : { - "timeCase" : "AGE", - "age" : { - "years" : 11, - "months" : null, - "days" : null - } - }, - "vitalStatus" : { - "status" : "ALIVE", - "timeOfDeath" : null - }, - "diseases" : [ { - "diseaseIdentifier" : { - "diseaseId" : "OMIM:176670", - "diseaseName" : "HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS" - }, - "isExcluded" : false - } ], - "genotypes" : [ { - "variantMd5Hex" : "a0b9ec70522aa63dd5d066d1326c8e8b", - "genotype" : "HETEROZYGOUS" - } ], - "phenotypicFeatures" : [ { - "termId" : "HP:0001072", - "label" : "Thickened skin", - "isExcluded" : false, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0001808", - "label" : "Fragile nails", - "isExcluded" : false, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0000278", - "label" : "Retrognathia", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0000164", - "label" : "Abnormality of the dentition", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0011025", - "label" : "Abnormal cardiovascular system physiology", - "isExcluded" : true, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0004322", - "label" : "Short stature", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : 4, - "months" : null, - "days" : null - } - }, - "resolution" : null - } ], - "sex" : "MALE" - } -} \ No newline at end of file diff --git a/data/LMNA/Bar_2017_27920058-DB423.json b/data/LMNA/Bar_2017_27920058-DB423.json deleted file mode 100644 index a7115022f..000000000 --- a/data/LMNA/Bar_2017_27920058-DB423.json +++ /dev/null @@ -1,158 +0,0 @@ -{ - "id" : "Bar_2017_27920058-DB423", - "studyMetadata" : { - "freeText" : "", - "createdBy" : { - "curatorId" : "HPO:ielis", - "softwareVersion" : "2.0.0-RC3-SNAPSHOT", - "timestamp" : "2023-03-20T19:18:35.056175814Z" - }, - "modifiedBy" : [ { - "curatorId" : "HPO:ielis", - "softwareVersion" : "2.0.0-RC3-SNAPSHOT", - "timestamp" : "2023-03-20T19:35:19.782258984Z" - } ] - }, - "publication" : { - "authors" : "Bar DZ, Arlt MF, Brazier JF, Norris WE, Campbell SE, Chines P, Larrieu D, Jackson SP, Collins FS, Glover TW, Gordon LB", - "title" : "A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.", - "journal" : "J Med Genet", - "year" : 2017, - "volume" : "54(3)", - "pages" : "212-216", - "pmid" : "27920058" - }, - "variants" : [ { - "variantType" : "SNV", - "genomicAssemblyAccession" : "GRCh38.p13", - "contigGenBankAccession" : "CM000663.2", - "strand" : "+", - "start" : 156138758, - "end" : 156138759, - "changeLength" : 0, - "id" : "nonclassic-HGPS-severe", - "md5Hex" : "9091726c38c3cb63e5e197e66df093e2", - "ref" : "T", - "alt" : "A", - "validationContext" : "VariantMetadataDefault", - "validationMetadata" : { - "variantMetadataContext" : "UNKNOWN", - "snippet" : null, - "variantClass" : "N/A", - "pathomechanism" : "N/A", - "cosegregation" : false, - "comparability" : false - } - } ], - "individual" : { - "id" : "DB423", - "age" : null, - "vitalStatus" : { - "status" : "DECEASED", - "timeOfDeath" : { - "timeCase" : "AGE", - "age" : { - "years" : 3, - "months" : 6, - "days" : null - } - } - }, - "diseases" : [ { - "diseaseIdentifier" : { - "diseaseId" : "OMIM:176670", - "diseaseName" : "HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS" - }, - "isExcluded" : false - } ], - "genotypes" : [ { - "variantMd5Hex" : "9091726c38c3cb63e5e197e66df093e2", - "genotype" : "HETEROZYGOUS" - } ], - "phenotypicFeatures" : [ { - "termId" : "HP:0008404", - "label" : "Nail dystrophy", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : null, - "days" : 0 - } - }, - "resolution" : null - }, { - "termId" : "HP:0009125", - "label" : "Lipodystrophy", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : null, - "days" : 0 - } - }, - "resolution" : null - }, { - "termId" : "HP:0100324", - "label" : "Scleroderma", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : null, - "days" : 0 - } - }, - "resolution" : null - }, { - "termId" : "HP:0001508", - "label" : "Failure to thrive", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : null, - "days" : 0 - } - }, - "resolution" : null - }, { - "termId" : "HP:0001596", - "label" : "Alopecia", - "isExcluded" : false, - "onset" : { - "timeCase" : "AGE", - "age" : { - "years" : null, - "months" : 3, - "days" : null - } - }, - "resolution" : null - }, { - "termId" : "HP:0000278", - "label" : "Retrognathia", - "isExcluded" : false, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0034392", - "label" : "Joint contracture", - "isExcluded" : false, - "onset" : null, - "resolution" : null - }, { - "termId" : "HP:0005177", - "label" : "Premature arteriosclerosis", - "isExcluded" : false, - "onset" : null, - "resolution" : null - } ], - "sex" : "FEMALE" - } -} \ No newline at end of file diff --git a/notebooks/LMNA/Bonne_LMNA_2000.ipynb b/notebooks/LMNA/Bonne_LMNA_2000.ipynb index 5b52137cb..f879c9029 100644 --- a/notebooks/LMNA/Bonne_LMNA_2000.ipynb +++ b/notebooks/LMNA/Bonne_LMNA_2000.ipynb @@ -103,6 +103,9 @@ " Neck\n", " Contracture\n", " Spine\n", + " Electrocardiography\n", + " Echocardiography\n", + " NM_170707.4\n", " \n", " \n", " \n", @@ -122,6 +125,9 @@ " stiff\n", " E,A\n", " Rigid\n", + " Pacemaker\n", + " Ventricular dysfunction\n", + " c.16C>T\n", " \n", " \n", " 1\n", @@ -139,6 +145,9 @@ " stiff\n", " E,A\n", " Rigid\n", + " Pacemaker\n", + " Ventricular dysfunction\n", + " c.16C>T\n", " \n", " \n", " 2\n", @@ -156,6 +165,9 @@ " N\n", " E,A\n", " Rigid\n", + " Arrhythmia\n", + " N\n", + " c.16C>T\n", " \n", " \n", " 3\n", @@ -173,6 +185,9 @@ " stiff\n", " A\n", " Rigid\n", + " Arrhythmia\n", + " N\n", + " c.16C>T\n", " \n", " \n", " 4\n", @@ -190,6 +205,9 @@ " stiff\n", " E,A\n", " Rigid\n", + " Pacemaker\n", + " N\n", + " c.16C>T\n", " \n", " \n", "\n", @@ -210,12 +228,19 @@ "3 Slowly progressive YD + na Scapuloperoneal \n", "4 Slowly progressive YD + 2 Scapuloperoneal \n", "\n", - " Weakness in Upper Limbs Weakness in Lower Limbs Neck Contracture Spine \n", - "0 Proximal NaN stiff E,A Rigid \n", - "1 Proximal NaN stiff E,A Rigid \n", - "2 Distal Proximal N E,A Rigid \n", - "3 Proximal NaN stiff A Rigid \n", - "4 Proximal NaN stiff E,A Rigid " + " Weakness in Upper Limbs Weakness in Lower Limbs Neck Contracture \\\n", + "0 Proximal NaN stiff E,A \n", + "1 Proximal NaN stiff E,A \n", + "2 Distal Proximal N E,A \n", + "3 Proximal NaN stiff A \n", + "4 Proximal NaN stiff E,A \n", + "\n", + " Spine Electrocardiography Echocardiography NM_170707.4 \n", + "0 Rigid Pacemaker Ventricular dysfunction c.16C>T \n", + "1 Rigid Pacemaker Ventricular dysfunction c.16C>T \n", + "2 Rigid Arrhythmia N c.16C>T \n", + "3 Rigid Arrhythmia N c.16C>T \n", + "4 Rigid Pacemaker N c.16C>T " ] }, "execution_count": 3, @@ -230,10 +255,534 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 4, "id": "a3affe8a-2dc5-471c-b7c1-7145806c3b88", "metadata": {}, "outputs": [], + "source": [ + "# Make the approximate assumption that childhood onset is P2Y\n", + "def iso_age(onset):\n", + " if onset.startswith(\"P\"):\n", + " return onset\n", + " elif onset == \"Childhood\":\n", + " return \"P2Y\"\n", + " elif onset == \"na\":\n", + " return \"n/a\"\n", + " else:\n", + " return f\"Could not map{onset}\"\n", + "\n", + "df['iso_onset'] = df[\"Onset\"].apply(lambda x: iso_age(x))\n", + "ageMapper = AgeColumnMapper.iso8601(column_name='iso_onset')\n", + "#ageMapper.preview_column(df['iso_onset'])\n", + "sexMapper = SexColumnMapper.not_provided()" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "11b8d095-97d6-4360-a2b4-a2abe611abe8", + "metadata": {}, + "outputs": [], + "source": [ + "def indiv_id(patient):\n", + " individual_id = patient\n", + " return individual_id.replace(\" \", \"_\")\n", + " \n", + "df['individual_id'] = df[\"Patient\"].apply(lambda x: indiv_id(x))" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "77df836b-bbe3-4b35-af0a-fa0a153b7262", + "metadata": {}, + "outputs": [], + "source": [ + "#res = OptionColumnMapper.autoformat(df=df, concept_recognizer=hpo_cr)\n", + "#print(res)\n", + "column_mapper_d = {}" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "id": "95c5c82b-08bf-438d-ac48-3ff570ba6990", + "metadata": {}, + "outputs": [], + "source": [ + "first_symptoms_d = {'Waddling gait': 'Waddling gait',\n", + " 'difficulty in running': 'Difficulty running',\n", + " 'AT contractures': 'Achilles tendon contracture',\n", + " 'Difficulty in climbing': 'Difficulty climbing stairs',\n", + " 'Difficulty in walking': 'Difficulty walking',\n", + " 'Difficulty in running': 'Difficulty running',\n", + " 'Elbow flexion': 'Elbow flexion contracture',\n", + " 'Weakness': 'Muscle weakness',\n", + " 'positive Gower sign': 'Gowers sign',\n", + " 'Frequent falls': 'Frequent falls',\n", + " 'Positive Gower sign': 'Gowers sign',\n", + " #'Difficulty in getting up': 'PLACEHOLDER',\n", + " 'Falling': 'Frequent falls',\n", + " 'fatigue': 'Fatigue',\n", + " 'Fatigue': 'Fatigue',\n", + " 'foot deformity': 'Abnormal foot morphology',\n", + " 'Minimal wasting': 'Skeletal muscle atrophy',\n", + " 'Delayed motor development': 'Motor delay'}\n", + "firstsymptomsMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=first_symptoms_d)\n", + "firstsymptomsMapper.preview_column(df['First Symptoms'])\n", + "column_mapper_d['First Symptoms'] = firstsymptomsMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "49911666-df6a-4cfc-ae83-be47e5b460bd", + "metadata": {}, + "outputs": [], + "source": [ + "walks_d = {'YD': 'Difficulty walking',\n", + " 'WCB(55)': 'Loss of ambulation',\n", + " 'WCB(13)': 'Loss of ambulation',\n", + " 'WCB(8)': 'Loss of ambulation'}\n", + "walksMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=walks_d)\n", + "walksMapper.preview_column(df['Walks(age [yr])'])\n", + "column_mapper_d['Walks(age [yr])'] = walksMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "id": "43dcbbe8-a908-4e9a-b4f3-66f1a386b511", + "metadata": {}, + "outputs": [], + "source": [ + "ck_d = {\n", + " '2': 'Elevated circulating creatine kinase concentration',\n", + " '3': 'Elevated circulating creatine kinase concentration',\n", + " '4': 'Highly elevated creatine kinase',\n", + " '5': 'Highly elevated creatine kinase',\n", + " '6': 'Highly elevated creatine kinase',\n", + " '7': 'Highly elevated creatine kinase',\n", + " '8': 'Highly elevated creatine kinase',\n", + " '15': 'Highly elevated creatine kinase',\n", + " '14': 'Highly elevated creatine kinase'}\n", + "excluded ={'N': 'Elevated circulating creatine kinase concentration',}\n", + "ckMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=ck_d, excluded_d=excluded)\n", + "ckMapper.preview_column(df['CK'])\n", + "column_mapper_d['CK'] = ckMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": "bfcb45f3-0fcf-4ce4-8363-d02710723d90", + "metadata": {}, + "outputs": [], + "source": [ + "wasting_d = {'Scapuloperoneal': 'Scapuloperoneal amyotrophy',\n", + " 'Scapular': 'Amyotrophy involving the shoulder musculature',\n", + " 'Mild distal': 'Distal amyotrophy',\n", + " 'pes cavus': 'Pes cavus',\n", + " 'Diffuse wasting': 'Distal amyotrophy',\n", + " 'preddistal': 'Distal amyotrophy',\n", + " 'Pseudohypertrophy calves': 'Calf muscle pseudohypertrophy',\n", + " 'Both arms': 'Upper limb amyotrophy',\n", + " 'Humeroperoneal': 'Proximal amyotrophy',\n", + " 'bilateral pes equinus': 'Talipes equinovarus',\n", + " 'Mild proximal': 'Proximal amyotrophy',\n", + " 'Proximal': 'Proximal amyotrophy',\n", + " 'scapular winging': 'Scapular winging',\n", + " 'Diffuse': 'Generalized amyotrophy',\n", + " #'Pseudohypertrophy in deltoideus': 'PLACEHOLDER', no term\n", + " 'wasting shoulder': 'Amyotrophy involving the shoulder musculature',\n", + " 'wasting leg': 'Lower limb amyotrophy',\n", + " 'Upper arms': 'Proximal upper limb amyotrophy',\n", + " 'glutei': 'Proximal lower limb amyotrophy',\n", + " 'Proximal muscle': 'Proximal amyotrophy',\n", + " 'upper arm': 'Upper limb amyotrophy',\n", + " 'leg': 'Lower limb amyotrophy',\n", + " 'Distal': 'Distal amyotrophy',\n", + " 'pes equinovarus': 'Talipes equinovarus',\n", + " 'legs': 'Lower limb amyotrophy',\n", + " 'Humeral': 'Proximal upper limb amyotrophy',\n", + " 'posterior leg': 'Lower limb amyotrophy',\n", + " 'upper leg': 'Proximal lower limb amyotrophy',\n", + " 'bilateral pes equinus': 'Bilateral talipes equinovarus'}\n", + "wastingMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=wasting_d)\n", + "wastingMapper.preview_column(df['Wasting'])\n", + "column_mapper_d['Wasting'] = wastingMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "id": "d592e50c-9eae-4c56-9466-7c11eab1633e", + "metadata": {}, + "outputs": [], + "source": [ + "weakness_upper_limbs_d = {'Proximal': 'Proximal muscle weakness in upper limbs',\n", + " 'Distal': 'Upper limb muscle weakness',\n", + " 'Mildly proximal': 'Proximal muscle weakness in upper limbs'}\n", + "weakness_upper_limbsMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=weakness_upper_limbs_d)\n", + "weakness_upper_limbsMapper.preview_column(df['Weakness in Upper Limbs'])\n", + "column_mapper_d['Weakness in Upper Limbs'] = weakness_upper_limbsMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "id": "e2e7e253-8f8d-4804-b04d-5e4ad54b9034", + "metadata": {}, + "outputs": [], + "source": [ + "weakness_lower_limbs_d = {\n", + " 'Proximal': 'Proximal muscle weakness in lower limbs',\n", + " 'Distal': 'Distal lower limb muscle weakness',\n", + " }\n", + "weakness_lower_limbsMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=weakness_lower_limbs_d)\n", + "weakness_lower_limbsMapper.preview_column(df['Weakness in Lower Limbs'])\n", + "column_mapper_d['Weakness in Lower Limbs'] = weakness_lower_limbsMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 13, + "id": "5367fdc6-0775-41a3-963e-3b0dcdaf839c", + "metadata": {}, + "outputs": [], + "source": [ + "neck_d = {'stiff': 'Stiff neck',\n", + "}\n", + "neckMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=neck_d)\n", + "neckMapper.preview_column(df['Neck'])\n", + "column_mapper_d['Neck'] = neckMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "id": "72852218-5653-4fd5-a165-dd3af967a01c", + "metadata": {}, + "outputs": [], + "source": [ + "# A: ankles; E: elbow; F: finger; H: hips; K: knee; W: wrist; N: normal; \n", + "contracture_d = {'E': 'Elbow contracture',\n", + " 'A': 'Ankle contracture',\n", + " 'K': 'Knee contracture',\n", + " 'H': 'Hip contracture',\n", + " 'W': 'Wrist flexion contracture',\n", + " 'F': 'Finger joint contracture'}\n", + "excluded = {'N':'Joint contracture' }\n", + "contractureMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=contracture_d, excluded_d=excluded)\n", + "contractureMapper.preview_column(df['Contracture'])\n", + "column_mapper_d['Contracture'] = contractureMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 15, + "id": "b47cb3d9-b721-472b-ae3a-3ad1e2d4dfd6", + "metadata": {}, + "outputs": [], + "source": [ + "spine_d = {'Rigid': 'Spinal rigidity',\n", + " 'Scoliosis': 'Scoliosis',\n", + " 'thoracic kyphosis': 'Thoracic kyphosis',\n", + " 'hyperext lordosis': 'Hyperlordosis'}\n", + "spineMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=spine_d)\n", + "spineMapper.preview_column(df['Spine'])\n", + "column_mapper_d['Spine'] = spineMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 16, + "id": "74ab44c6-7ccf-461a-bc65-81b5956618f9", + "metadata": {}, + "outputs": [], + "source": [ + "# Six pa-tients had a pacemaker inserted (age range, 35– 61years), and 1 patient (Spo1) had an implantable defi-brillator inserted for \n", + "# severe ventricular dysrhythmias duringel ectrophysiological testing.\n", + "ecg_d = {'Pacemaker': 'Ventricular arrhythmia',\n", + " 'Arrhythmia': 'Arrhythmia'}\n", + "ecgMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=ecg_d)\n", + "ecgMapper.preview_column(df['Electrocardiography'])\n", + "column_mapper_d['Electrocardiography'] = ecgMapper" + ] + }, + { + "cell_type": "code", + "execution_count": 17, + "id": "abd09d41-d82d-4837-9d92-a9ba88503579", + "metadata": {}, + "outputs": [], + "source": [ + "echo_d = {'Ventricular dysfunction': 'Abnormal left ventricular function'}\n", + "excluded = {'N': 'Abnormal left ventricular function'}\n", + "echoMapper = OptionColumnMapper(concept_recognizer=hpo_cr, option_d=echo_d, excluded_d=excluded)\n", + "echoMapper.preview_column(df['Echocardiography'])\n", + "column_mapper_d['Echocardiography'] = echoMapper" + ] + }, + { + "cell_type": "markdown", + "id": "f59f2327-af1f-4817-9d83-255c6adfd9af", + "metadata": {}, + "source": [ + "# Variants\n", + "\n", + "We mapped the variants to HGNC nomenclature as follows\n", + "\n", + "- EMD1 CAG -> TAG Q6Stop: NM_170707.4(LMNA):c.16C>T (p.Gln6Ter) \n", + "- Spo3 TAC -> TGC Y45C: NM_170707.4(LMNA):c.134A>G (p.Tyr45Cys) \n", + "- Spo27 CGC -> CCC R50P: NM_170707.4(LMNA):c.149G>C (p.Arg50Pro) \n", + "- Spo104 ATC ->AGC I63S: NM_170707.4(LMNA):c.188T>G (p.Ile63Ser) \n", + "- Spo20 delGAG del112: NM_170707.4(LMNA):c.334_336del (p.Glu112del)\n", + "- EMD3 CAT -> CCT H222P: NM_170707.4(LMNA):c.665A>C (p.His222Pro)\n", + "- Spo70 GGG ->GAG G232E: NM_170707.4(LMNA):c.695G>A (p.Gly232Glu) \n", + "- Spo89 CGG -> CAG R249Q: NM_170707.4(LMNA):c.746G>A (p.Arg249Gln)\n", + "- Spo1 delAAG delK261: NM_170707.4:c.781_783del/NP_733821.1:p.(Lys261del)\n", + "- Spo2 CAG ->CCG Q294P: NM_170707.4(LMNA):c.881A>C (p.Gln294Pro)\n", + "- Spo11 GAG -> AAG E358K: NM_170707.4(LMNA):c.1072G>A (p.Glu358Lys)\n", + "- Spo69 GAG -> AAG E358K: NM_170707.4(LMNA):c.1072G>A (p.Glu358Lys)\n", + "- Spo10 ATG -> AAG M371K: NM_170707.4(LMNA):c.1112T>A (p.Met371Lys)\n", + "- EMD5 AG/G -> AA/G R386K+intron 6: NM_170707.4(LMNA):c.1157G>A (p.Arg386Lys)\n", + "- Spo47 CGG -> TGG R453W: NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp)\n", + "- Spo37 CGG -> TGG R453W: NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp)\n", + "- EMD2 CGG -> TGG R453W: NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp)\n", + "- Spo78 AAC -> AAA N456K: NM_170707.4(LMNA):c.1368C>A (p.Asn456Lys)\n", + "- Spo21 TGG -> TCG W520S: NM_170707.4(LMNA):c.1559G>C (p.Trp520Ser)\n", + "- EMD6 CGT -> CCT R527P: NM_170707.4(LMNA):c.1580G>C (p.Arg527Pro)\n", + "- EMD4 CGT -> CCT R527P: NM_170707.4(LMNA):c.1580G>C (p.Arg527Pro)\n", + "- Spo28 ACG -> AAG T528K: NM_170707.4(LMNA):c.1583C>A (p.Thr528Lys)\n", + "- Spo29 ACG -> AAG T528K: NM_170707.4(LMNA):c.1583C>A (p.Thr528Lys)" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "id": "de77bc76-c6ef-43dd-b157-f910704048c9", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.16C>T/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.134A>G/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.149G>C/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.188T>G/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.334_336del/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.665A>C/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.695G>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.746G>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.781_783del/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.881A>C/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1072G>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1112T>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1157G>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1357C>T/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1368C>A/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1559G>C/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1580G>C/NM_005572.4?content-type=application%2Fjson\n", + "https://rest.variantvalidator.org/VariantValidator/variantvalidator/hg38/NM_005572.4%3Ac.1583C>A/NM_005572.4?content-type=application%2Fjson\n" + ] + } + ], + "source": [ + "LMNA_transcript = \"NM_005572.4\"\n", + "vvalidator = VariantValidator(genome_build=\"hg38\", transcript=LMNA_transcript)\n", + "var_d = {}\n", + "for v in df['NM_170707.4'].unique():\n", + " var = vvalidator.encode_hgvs(v)\n", + " var.set_heterozygous()\n", + " var_d[v] = var" + ] + }, + { + "cell_type": "code", + "execution_count": 19, + "id": "748aa16b-ad98-4b10-8e75-e22c997a988d", + "metadata": {}, + "outputs": [], + "source": [ + "varMapper = VariantColumnMapper(variant_d=var_d, variant_column_name='NM_170707.4', default_genotype='heterozygous')\n", + "encoder = CohortEncoder(df=df, \n", + " hpo_cr=hpo_cr, \n", + " column_mapper_d=column_mapper_d, \n", + " individual_column_name=\"individual_id\", \n", + " agemapper=ageMapper, \n", + " variant_mapper=varMapper,\n", + " sexmapper=sexMapper,\n", + " metadata=metadata)\n", + "omim_id = \"OMIM:181350\"\n", + "omim_label = \"Emery-Dreifuss muscular dystrophy 2, autosomal dominant\" \n", + "edmd2 = Disease(disease_id=omim_id, disease_label=omim_label)\n", + "encoder.set_disease(disease=edmd2)" + ] + }, + { + "cell_type": "code", + "execution_count": 20, + "id": "a87e1dc7-ee19-4a7c-b514-e8a9063a914b", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Could not parse the following as ISO8601 ages: n/a (n=1)\n" + ] + }, + { + "data": { + "text/html": [ + "

Cohort validation

\n", + "

Errors found with 21 of 41 phenopackets.

\n", + "\n", + "\n", + "\n", + "\n", + "
Error counts
LevelError categoryCount
WARNINGREDUNDANT22
\n", + "

A total of 24 issues were fixed and no individual was removed from the cohort.

" + ], + "text/plain": [ + "" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "individuals = encoder.get_individuals()\n", + "cvalidator = CohortValidator(cohort=individuals, ontology=hpo_ontology, min_hpo=1, allelic_requirement=AllelicRequirement.MONO_ALLELIC)\n", + "qc = QcVisualizer(cohort_validator=cvalidator)\n", + "display(HTML(qc.to_summary_html()))" + ] + }, + { + "cell_type": "code", + "execution_count": 21, + "id": "ad5ae6a4-e5b2-4f70-a125-e1c78805d89c", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "\n", + "
41 phenopackets - PMID:10939567 (n=41)
IndividualDiseaseGenotypePhenotypic features
EMD1_III-2 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.16C>T (heterozygous)Waddling gait (HP:0002515); Difficulty running (HP:0009046); Difficulty walking (HP:0002355); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); Abnormal left ventricular function (HP:0005162)
EMD1_III-20 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.16C>T (heterozygous)Waddling gait (HP:0002515); Difficulty running (HP:0009046); Loss of ambulation (HP:0002505); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); Abnormal left ventricular function (HP:0005162)
EMD1_IV-13 (UNKNOWN; P15Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.16C>T (heterozygous)Achilles tendon contracture (HP:0001771); Difficulty running (HP:0009046); Difficulty walking (HP:0002355); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Upper limb muscle weakness (HP:0003484); Proximal muscle weakness in lower limbs (HP:0008994); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD1_IV-14 (UNKNOWN; )Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.16C>T (heterozygous)Difficulty climbing stairs (HP:0003551); Difficulty walking (HP:0002355); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD1_IV-24 (UNKNOWN; P15Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.16C>T (heterozygous)Achilles tendon contracture (HP:0001771); Difficulty walking (HP:0002355); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); excluded: Abnormal left ventricular function (HP:0005162)
Spo3 (UNKNOWN; P6Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.134A>G (heterozygous)Difficulty walking (HP:0002355); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Knee contracture (HP:0034671); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
Spo27 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.149G>C (heterozygous)Difficulty walking (HP:0002355); Loss of ambulation (HP:0002505); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Knee contracture (HP:0034671); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
Spo104 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.188T>G (heterozygous)Difficulty running (HP:0009046); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Wrist flexion contracture (HP:0001239); Finger joint contracture (HP:0034681); Knee contracture (HP:0034671); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162)
Spo20 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.334_336del (heterozygous)Difficulty running (HP:0009046); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Finger joint contracture (HP:0034681); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
EMD3_III-3 (UNKNOWN; P1D)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.665A>C (heterozygous)Elbow flexion contracture (HP:0002987); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675)
EMD3_IV-5 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.665A>C (heterozygous)Elbow flexion contracture (HP:0002987); Amyotrophy involving the shoulder musculature (HP:0001465); Stiff neck (HP:0025258); Ankle contracture (HP:0034677); Scoliosis (HP:0002650)
EMD3_IV-7 (UNKNOWN; P5Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.665A>C (heterozygous)Achilles tendon contracture (HP:0001771); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
Spo70 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.695G>A (heterozygous)Gowers sign (HP:0003391); Loss of ambulation (HP:0002505); Highly elevated creatine kinase (HP:0030234); Distal amyotrophy (HP:0003693); Pes cavus (HP:0001761); Proximal muscle weakness in upper limbs (HP:0008997); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Wrist flexion contracture (HP:0001239); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
Spo89 (UNKNOWN; P8Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.746G>A (heterozygous)Difficulty walking (HP:0002355); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Distal lower limb muscle weakness (HP:0009053); Elbow contracture (HP:0034391); Wrist flexion contracture (HP:0001239); Knee contracture (HP:0034671); Ankle contracture (HP:0034677); Arrhythmia (HP:0011675); excluded: Elevated circulating creatine kinase concentration (HP:0003236); excluded: Abnormal left ventricular function (HP:0005162)
Spo1 (UNKNOWN; P3Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.781_783del (heterozygous)Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Stiff neck (HP:0025258); Highly elevated creatine kinase (HP:0030234); Elbow contracture (HP:0034391); Difficulty walking (HP:0002355); Upper limb muscle weakness (HP:0003484); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162); Distal lower limb muscle weakness (HP:0009053); Proximal muscle weakness in lower limbs (HP:0008994); Distal amyotrophy (HP:0003693)
Spo2 (UNKNOWN; P5Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.881A>C (heterozygous)Frequent falls (HP:0002359); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162); excluded: Elevated circulating creatine kinase concentration (HP:0003236)
Spo11 (UNKNOWN; P1Y1M)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1072G>A (heterozygous)Highly elevated creatine kinase (HP:0030234); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
Spo69 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1072G>A (heterozygous)Difficulty walking (HP:0002355); Elevated circulating creatine kinase concentration (HP:0003236); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162)
Spo10 (UNKNOWN; P21Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1112T>A (heterozygous)Difficulty climbing stairs (HP:0003551); Difficulty walking (HP:0002355); Elevated circulating creatine kinase concentration (HP:0003236); Amyotrophy involving the shoulder musculature (HP:0001465); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); excluded: Abnormal left ventricular function (HP:0005162)
EMD5_II-1 (UNKNOWN; P7Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1157G>A (heterozygous)Frequent falls (HP:0002359); Elevated circulating creatine kinase concentration (HP:0003236); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); Abnormal left ventricular function (HP:0005162)
EMD5_III-3 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1157G>A (heterozygous)Waddling gait (HP:0002515); Achilles tendon contracture (HP:0001771); Highly elevated creatine kinase (HP:0030234); Calf muscle pseudohypertrophy (HP:0003707); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD5_III-4 (UNKNOWN; P5Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1157G>A (heterozygous)Waddling gait (HP:0002515); Amyotrophy involving the shoulder musculature (HP:0001465); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD5_III-5 (UNKNOWN; P6Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1157G>A (heterozygous)Gowers sign (HP:0003391); Elevated circulating creatine kinase concentration (HP:0003236); Amyotrophy involving the shoulder musculature (HP:0001465); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); excluded: Abnormal left ventricular function (HP:0005162)
Spo4 (UNKNOWN; P3Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Difficulty running (HP:0009046); Highly elevated creatine kinase (HP:0030234); Upper limb amyotrophy (HP:0009129); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162)
Spo37 (UNKNOWN; P8Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Difficulty climbing stairs (HP:0003551); Elevated circulating creatine kinase concentration (HP:0003236); Proximal amyotrophy (HP:0007126); Bilateral talipes equinovarus (HP:0001776); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Ventricular arrhythmia (HP:0004308); excluded: Abnormal left ventricular function (HP:0005162)
EMD2_II-3 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Difficulty running (HP:0009046); Difficulty walking (HP:0002355); Proximal amyotrophy (HP:0007126); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Scoliosis (HP:0002650); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD2_II-4 (UNKNOWN; P40Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Difficulty running (HP:0009046); Difficulty walking (HP:0002355); Proximal amyotrophy (HP:0007126); Scapular winging (HP:0003691); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Scoliosis (HP:0002650); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD2_III-6 (UNKNOWN; P3Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Highly elevated creatine kinase (HP:0030234); Scapuloperoneal amyotrophy (HP:0003697); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
EMD2_III-7 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1357C>T (heterozygous)Generalized amyotrophy (HP:0003700); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
Spo78 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1368C>A (heterozygous)Gowers sign (HP:0003391); Loss of ambulation (HP:0002505); Highly elevated creatine kinase (HP:0030234); Generalized amyotrophy (HP:0003700); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Knee contracture (HP:0034671); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
Spo21 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1559G>C (heterozygous)Frequent falls (HP:0002359); Fatigue (HP:0012378); Difficulty walking (HP:0002355); Highly elevated creatine kinase (HP:0030234); Amyotrophy involving the shoulder musculature (HP:0001465); Lower limb amyotrophy (HP:0007210); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Thoracic kyphosis (HP:0002942); Arrhythmia (HP:0011675); Abnormal left ventricular function (HP:0005162)
EMD6_II-3 (UNKNOWN; P40Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Fatigue (HP:0012378); Elevated circulating creatine kinase concentration (HP:0003236); Proximal upper limb amyotrophy (HP:0008948); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675)
EMD6_III-5 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Waddling gait (HP:0002515); Elevated circulating creatine kinase concentration (HP:0003236); Upper limb amyotrophy (HP:0009129); Lower limb amyotrophy (HP:0007210); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD6_IV-7 (UNKNOWN; P3Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Difficulty walking (HP:0002355); Highly elevated creatine kinase (HP:0030234); Distal amyotrophy (HP:0003693); Talipes equinovarus (HP:0001762); Pes cavus (HP:0001761); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Hip contracture (HP:0003273); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD4_II-2 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Difficulty running (HP:0009046); Difficulty walking (HP:0002355); Highly elevated creatine kinase (HP:0030234); Proximal upper limb amyotrophy (HP:0008948); Lower limb amyotrophy (HP:0007210); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD4_III-4 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Frequent falls (HP:0002359); Fatigue (HP:0012378); Difficulty walking (HP:0002355); Highly elevated creatine kinase (HP:0030234); Proximal upper limb amyotrophy (HP:0008948); Lower limb amyotrophy (HP:0007210); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Scoliosis (HP:0002650); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
EMD4_III-6 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Frequent falls (HP:0002359); Fatigue (HP:0012378); Highly elevated creatine kinase (HP:0030234); Proximal upper limb amyotrophy (HP:0008948); Lower limb amyotrophy (HP:0007210); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Scoliosis (HP:0002650); excluded: Abnormal left ventricular function (HP:0005162)
EMD4_III-7 (UNKNOWN; P4Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Frequent falls (HP:0002359); Fatigue (HP:0012378); Highly elevated creatine kinase (HP:0030234); Proximal upper limb amyotrophy (HP:0008948); Lower limb amyotrophy (HP:0007210); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); excluded: Abnormal left ventricular function (HP:0005162)
EMD4_III-8 (UNKNOWN; P15Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1580G>C (heterozygous)Highly elevated creatine kinase (HP:0030234); Proximal upper limb amyotrophy (HP:0008948); Lower limb amyotrophy (HP:0007210); Proximal lower limb amyotrophy (HP:0008956); Proximal muscle weakness in upper limbs (HP:0008997); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306)
Spo28 (UNKNOWN; P2Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1583C>A (heterozygous)Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Hyperlordosis (HP:0003307); Highly elevated creatine kinase (HP:0030234); Fatigue (HP:0012378); Elbow contracture (HP:0034391); Difficulty walking (HP:0002355); Proximal muscle weakness in upper limbs (HP:0008997); Arrhythmia (HP:0011675); Distal lower limb muscle weakness (HP:0009053); Proximal muscle weakness in lower limbs (HP:0008994); Distal amyotrophy (HP:0003693); Hip contracture (HP:0003273)
Spo29 (UNKNOWN; P1Y)Emery-Dreifuss muscular dystrophy 2, autosomal dominant (OMIM:181350)NM_005572.4:c.1583C>A (heterozygous)Motor delay (HP:0001270); Fatigue (HP:0012378); Highly elevated creatine kinase (HP:0030234); Upper limb amyotrophy (HP:0009129); Proximal lower limb amyotrophy (HP:0008956); Bilateral talipes equinovarus (HP:0001776); Proximal muscle weakness in upper limbs (HP:0008997); Proximal muscle weakness in lower limbs (HP:0008994); Distal lower limb muscle weakness (HP:0009053); Stiff neck (HP:0025258); Elbow contracture (HP:0034391); Ankle contracture (HP:0034677); Spinal rigidity (HP:0003306); Arrhythmia (HP:0011675); excluded: Abnormal left ventricular function (HP:0005162)
" + ], + "text/plain": [ + "" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "individuals = cvalidator.get_error_free_individual_list()\n", + "table = PhenopacketTable(individual_list=individuals, metadata=metadata)\n", + "display(HTML(table.to_html()))" + ] + }, + { + "cell_type": "code", + "execution_count": 22, + "id": "58064f8d-8a41-40eb-a590-19cbe68697a9", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "Index(['Patient', 'Age', 'Onset', 'First Symptoms', 'Course',\n", + " 'Walks(age [yr])', 'Severity', 'CK', 'Wasting',\n", + " 'Weakness in Upper Limbs', 'Weakness in Lower Limbs', 'Neck',\n", + " 'Contracture', 'Spine', 'Electrocardiography', 'Echocardiography',\n", + " 'NM_170707.4', 'iso_onset', 'individual_id'],\n", + " dtype='object')" + ] + }, + "execution_count": 22, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "df.columns" + ] + }, + { + "cell_type": "code", + "execution_count": 23, + "id": "14679244-1ba5-4037-b9f3-5bf31280140a", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "array(['Pacemaker', 'Arrhythmia', 'N'], dtype=object)" + ] + }, + "execution_count": 23, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "df['Electrocardiography'].unique()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "c3f1ae72-55a8-43d8-a78c-0f857e90328f", + "metadata": {}, + "outputs": [], "source": [] } ], diff --git a/notebooks/LMNA/Brodsky2000_LMNA.ipynb b/notebooks/LMNA/Brodsky2000_LMNA.ipynb index af8550d98..4d800bbec 100644 --- a/notebooks/LMNA/Brodsky2000_LMNA.ipynb +++ b/notebooks/LMNA/Brodsky2000_LMNA.ipynb @@ -368,25 +368,6 @@ "column_mapper_d = {}" ] }, - { - "cell_type": "code", - "execution_count": 19, - "id": "97fb5918-dc91-45ff-95cf-dd87653c373a", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "array([2, 3, 1], dtype=object)" - ] - }, - "execution_count": 19, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [] - }, { "cell_type": "code", "execution_count": 22, diff --git a/notebooks/LMNA/input/Bonne2000.tsv b/notebooks/LMNA/input/Bonne2000.tsv index deb01aca1..de809440c 100644 --- a/notebooks/LMNA/input/Bonne2000.tsv +++ b/notebooks/LMNA/input/Bonne2000.tsv @@ -1,41 +1,42 @@ -Patient Age Onset First Symptoms Course Walks(age [yr]) Severity CK Wasting Weakness in Upper Limbs Weakness in Lower Limbs Neck Contracture Spine -EMD1 III-2 51 Childhood "Waddling gait,difficulty in running" Slowly progressive YD ++ na Scapuloperoneal Proximal stiff "E,A" Rigid -EMD1 III-20 61 Childhood "Waddling gait,difficulty in running" Slowly progressive WCB(55) ++ 2 Scapuloperoneal Proximal stiff "E,A" Rigid -EMD1 IV-13 48 P15Y "AT contractures, difficulty in running" Slowly progressive YD + 2 Scapuloperoneal Distal Proximal N "E,A" Rigid -EMD1 IV-14 46 na Difficulty in climbing Slowly progressive YD + na Scapuloperoneal Proximal stiff A Rigid -EMD1 IV-24 41 P15Y AT contractures Slowly progressive YD + 2 Scapuloperoneal Proximal stiff "E,A" Rigid -Spo3 18 P6Y Difficulty in walking Slowly progressive Y ++ 2 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,K,A" Rigid -Spo27 28 P2Y Difficulty in walking Progressive WCB(13) +++ na Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,H,K" Rigid -Spo104 31 P4Y Difficulty in running Progressive Y +++ 3 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,W,F,K,A" Rigid -Spo20 19 P4Y Difficulty in running Slowly progressive Y ++ 3 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,F,H,A" Rigid -EMD3 III-3 58 P1D Elbow flexion Slowly progressive Y ++ na Scapular "Proximal,Distal" "Proximal,Distal" stiff "E,A" Rigid -EMD3 IV-5 25 Childhood "Elbow flexion, spine" Slowly progressive Y ++ na Scapular stiff "E,A" Scoliosis -EMD3 IV-7 23 P5Y AT contractures Slowly progressive Y ++ na Scapular "Proximal,Distal" "Proximal,Distal" stiff "E,A" Rigid -Spo70 11 P2Y "Weakness,positive Gower sign" Progressive WCB(8) +++ 6 "Mild distal, pes cavus" "Proximal,Distal" Distal stiff "E,W,H,A" Rigid -Spo89 16 P8Y Difficulty in walking Slowly progressive Y ++ N Scapuloperoneal "Proximal,Distal" Distal N "E,W,K,A" N -Spo1 16 P3Y Difficulty in walking Slowly progressive Y ++ 5 "Diffuse wasting, preddistal" Distal "Proximal,Distal" stiff "E,A" Rigid -Spo2 26 P5Y Frequent falls Slowly progressive Y ++ N Scapular Proximal stiff "E,A" Rigid -Spo11 4 P1Y1M Feet posture Progressive Y +++ 5 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff A Rigid -Spo69 46 P21Y Difficulty in climbing Slowly progressive YD ++ 3 Scapular stiff E Rigid -EMD5 II-1 35 P7Y Frequent falls Slowly progressive Y ++ 3 Scapular Proximal "Proximal,Distal" stiff "E,A" Rigid -EMD5 III-3 11 P4Y "Waddling gait,AT contractionds" Slowly progressive Y ++ 4 "Pseudohypertrophy calves,Scapular" "Proximal,Distal" stiff "E,A" Rigid -EMD5 III-4 11 P5Y "Waddling gait,AT contractionds" Slowly progressive Y ++ na Scapular "Proximal,Distal" stiff "E,A" Rigid -EMD5 III-5 8 P6Y Positive Gower sign Slowly progressive Y + 3 Sc na N "E,A" na -Spo4 19 P3Y Difficulty in running Slowly progressive Y ++ 7 Both arms "Proximal,Distal" "Proximal,Distal" stiff "E,H,A" Rigid -Spo37 33 P8Y Difficulty in climbing Slowly progressive Y ++ 3 "Humeroperoneal,bilateral pes equinus" Proximal "Proximal,Distal" stiff "E,H,A" Rigid -EMD2 II-3 39 P4Y Difficulty in running Slowly progressive YD ++ na Mild proximal Proximal Proximal stiff "E,H,A" "Rigid,Scoliosis" -EMD2 II-4 40 40 Difficulty in running Slowly progressive YD ++ na "Proximal, scapular winging" Proximal Proximal stiff "E,H,A" "Rigid,Scoliosis" -EMD2 III-6 9 P3Y Difficulty in getting up Slowly progressive Y ++ 15 Scapuloperoneal Proximal "Proximal,Distal" stiff "E,A" Rigid -EMD2 III-7 7 P4Y Difficulty in getting up Slowly progressive Y +++ na Diffuse "Proximal,Distal" Proximal stiff "E,A" Rigid -Spo78 16 P2Y Positive Gower sign WCB(13) +++ 7 Diffuse Proximal Proximal stiff "E,H,K,A" Rigid -Spo21 25 P4Y "Falling,fatigue" Slowly progressive YD ++ 4 "Pseudohypertrophy in deltoidues, wasting shoulder, wasting leg" Proximal "Proximal,Distal" stiff "E,A" "Rigid,thoracic kyphosis" -EMD6 II-3 65 P40Y Fatigue Slowly progressive Y + 2 "Upper arms, glutei" Proximal Distal stiff "E,H,A" Rigid -EMD6 III-5 34 Childhood Waddling gait Slowly progressive Y ++ 2 "Proximal muscle,upper arm,leg,glutei" Proximal "Proximal,Distal" stiff "E,H,A" Rigid -EMD6 IV-7 17 P3Y "Difficulty in walking,foot deformity" Slowly progressive Y ++ 6 "Distal,pes equinovarus, pes cavus" N Distal stiff "E,H,A" Rigid -EMD4 II-2 50 Childhood Difficulty in running Slowly progressive YD ++ 4 "Upper arms, legs,glutei" Proximal stiff "E,A" Rigid -EMD4 III-4 24 P4Y "Falling,fatigue" Slowly progressive YD ++ 4 "Upper arms, legs,glutei" "Proximal,Distal" Distal stiff "E,A" Scoliosis -EMD4 III-6 20 P4Y "Falling,fatigue" Slowly progressive Y + 8 "Humeral, posterior leg" Proximal stiff "E,A" Scoliosis -EMD4 III-7 14 P4Y "Falling,fatigue" Slowly progressive Y ++ 5 "Upper arms, legs,glutei" Proximal stiff "E,A" Rigid -EMD4 III-8 12 P15Y Minimal wasting Slowly progressive Y ++ 14 "Upper arms, legs,glutei" Proximal N "E,A" Rigid -Spo28 36 P2Y "Fatigue, multiple sclerosis since 18y" Slowly progressive YD ++ 5 "Diffuse wasting, preddistal" "Proximal,Distal" "Proximal,Distal" Hyperext "E,A,H" "Rigid, hyperext lordosis" -Spo29 17 P1Y "Delayed motor development, fatigue" Slowly progressive Y ++ 5 "upper arm, upper leg, bilateral pes euinus" Mildly proximal "Proximal,Distal" stiff "E,A" Rigid \ No newline at end of file +Patient Age Onset First Symptoms Course Walks(age [yr]) Severity CK Wasting Weakness in Upper Limbs Weakness in Lower Limbs Neck Contracture Spine Electrocardiography Echocardiography NM_170707.4 +EMD1 III-2 51 Childhood "Waddling gait,difficulty in running" Slowly progressive YD ++ na Scapuloperoneal Proximal stiff "E,A" Rigid Pacemaker Ventricular dysfunction c.16C>T +EMD1 III-20 61 Childhood "Waddling gait,difficulty in running" Slowly progressive WCB(55) ++ 2 Scapuloperoneal Proximal stiff "E,A" Rigid Pacemaker Ventricular dysfunction c.16C>T +EMD1 IV-13 48 P15Y "AT contractures, difficulty in running" Slowly progressive YD + 2 Scapuloperoneal Distal Proximal N "E,A" Rigid Arrhythmia N c.16C>T +EMD1 IV-14 46 na Difficulty in climbing Slowly progressive YD + na Scapuloperoneal Proximal stiff A Rigid Arrhythmia N c.16C>T +EMD1 IV-24 41 P15Y AT contractures Slowly progressive YD + 2 Scapuloperoneal Proximal stiff "E,A" Rigid Pacemaker N c.16C>T +Spo3 18 P6Y Difficulty in walking Slowly progressive Y ++ 2 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,K,A" Rigid N N c.134A>G +Spo27 28 P2Y Difficulty in walking Progressive WCB(13) +++ na Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,H,K" Rigid Arrhythmia N c.149G>C +Spo104 31 P4Y Difficulty in running Progressive Y +++ 3 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,W,F,K,A" Rigid Arrhythmia Ventricular dysfunction c.188T>G +Spo20 19 P4Y Difficulty in running Slowly progressive Y ++ 3 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff "E,F,H,A" Rigid N N c.334_336del +EMD3 III-3 58 P1D Elbow flexion Slowly progressive Y ++ na Scapular "Proximal,Distal" "Proximal,Distal" stiff "E,A" Rigid Arrhythmia na c.665A>C +EMD3 IV-5 25 Childhood "Elbow flexion, spine" Slowly progressive Y ++ na Scapular stiff "E,A" Scoliosis N na c.665A>C +EMD3 IV-7 23 P5Y AT contractures Slowly progressive Y ++ na Scapular "Proximal,Distal" "Proximal,Distal" stiff "E,A" Rigid Arrhythmia N c.665A>C +Spo70 11 P2Y "Weakness,positive Gower sign" Progressive WCB(8) +++ 6 "Mild distal, pes cavus" "Proximal,Distal" Distal stiff "E,W,H,A" Rigid N N c.695G>A +Spo89 16 P8Y Difficulty in walking Slowly progressive Y ++ N Scapuloperoneal "Proximal,Distal" Distal N "E,W,K,A" N Arrhythmia N c.746G>A +Spo1 16 P3Y Difficulty in walking Slowly progressive Y ++ 5 "Diffuse wasting, preddistal" Distal "Proximal,Distal" stiff "E,A" Rigid Arrhythmia Ventricular dysfunction c.781_783del +Spo2 26 P5Y Frequent falls Slowly progressive Y ++ N Scapular Proximal stiff "E,A" Rigid Arrhythmia Ventricular dysfunction c.881A>C +Spo11 4 P1Y1M Feet posture Progressive Y +++ 5 Scapuloperoneal "Proximal,Distal" "Proximal,Distal" stiff A Rigid N N c.1072G>A +Spo69 23 P4Y Difficulty in walking Slowly progressive Y ++ 2 Scapuloperoneal "Proximal,Distal" stiff "E,H,A" Rigid Arrhythmia Ventricular dysfunction c.1072G>A +Spo10 46 P21Y Difficulty in climbing Slowly progressive YD ++ 3 Scapular stiff E Rigid Pacemaker N c.1112T>A +EMD5 II-1 35 P7Y Frequent falls Slowly progressive Y ++ 3 Scapular Proximal "Proximal,Distal" stiff "E,A" Rigid Pacemaker Ventricular dysfunction c.1157G>A +EMD5 III-3 11 P4Y "Waddling gait,AT contractures" Slowly progressive Y ++ 4 "Pseudohypertrophy calves,Scapular" "Proximal,Distal" stiff "E,A" Rigid Arrhythmia N c.1157G>A +EMD5 III-4 11 P5Y "Waddling gait,AT contractionds" Slowly progressive Y ++ na Scapular "Proximal,Distal" stiff "E,A" Rigid Arrhythmia N c.1157G>A +EMD5 III-5 8 P6Y Positive Gower sign Slowly progressive Y + 3 Scapular na N "E,A" na N N c.1157G>A +Spo4 19 P3Y Difficulty in running Slowly progressive Y ++ 7 Both arms "Proximal,Distal" "Proximal,Distal" stiff "E,H,A" Rigid Arrhythmia Ventricular dysfunction c.1357C>T +Spo37 33 P8Y Difficulty in climbing Slowly progressive Y ++ 3 "Humeroperoneal,bilateral pes equinus" Proximal "Proximal,Distal" stiff "E,H,A" Rigid Pacemaker N c.1357C>T +EMD2 II-3 39 P4Y Difficulty in running Slowly progressive YD ++ na Mild proximal Proximal Proximal stiff "E,H,A" "Rigid,Scoliosis" Arrhythmia N c.1357C>T +EMD2 II-4 40 P40Y Difficulty in running Slowly progressive YD ++ na "Proximal, scapular winging" Proximal Proximal stiff "E,H,A" "Rigid,Scoliosis" Arrhythmia N c.1357C>T +EMD2 III-6 9 P3Y Difficulty in getting up Slowly progressive Y ++ 15 Scapuloperoneal Proximal "Proximal,Distal" stiff "E,A" Rigid N N c.1357C>T +EMD2 III-7 7 P4Y Difficulty in getting up Slowly progressive Y +++ na Diffuse "Proximal,Distal" Proximal stiff "E,A" Rigid N N c.1357C>T +Spo78 16 P2Y Positive Gower sign WCB(13) +++ 7 Diffuse Proximal Proximal stiff "E,H,K,A" Rigid N N c.1368C>A +Spo21 25 P4Y "Falling,fatigue" Slowly progressive YD ++ 4 "Pseudohypertrophy in deltoideus, wasting shoulder, wasting leg" Proximal "Proximal,Distal" stiff "E,A" "Rigid,thoracic kyphosis" Arrhythmia Ventricular dysfunction c.1559G>C +EMD6 II-3 65 P40Y Fatigue Slowly progressive Y + 2 "Upper arms, glutei" Proximal Distal stiff "E,H,A" Rigid Arrhythmia na c.1580G>C +EMD6 III-5 34 Childhood Waddling gait Slowly progressive Y ++ 2 "Proximal muscle,upper arm,leg,glutei" Proximal "Proximal,Distal" stiff "E,H,A" Rigid Arrhythmia N c.1580G>C +EMD6 IV-7 17 P3Y "Difficulty in walking,foot deformity" Slowly progressive Y ++ 6 "Distal,pes equinovarus, pes cavus" N Distal stiff "E,H,A" Rigid Arrhythmia N c.1580G>C +EMD4 II-2 50 Childhood Difficulty in running Slowly progressive YD ++ 4 "Upper arms, legs,glutei" Proximal stiff "E,A" Rigid Arrhythmia N c.1580G>C +EMD4 III-4 24 P4Y "Falling,fatigue" Slowly progressive YD ++ 4 "Upper arms, legs,glutei" "Proximal,Distal" Distal stiff "E,A" Scoliosis Arrhythmia N c.1580G>C +EMD4 III-6 20 P4Y "Falling,fatigue" Slowly progressive Y + 8 "Humeral, posterior leg" Proximal stiff "E,A" Scoliosis N N c.1580G>C +EMD4 III-7 14 P4Y "Falling,fatigue" Slowly progressive Y ++ 5 "Upper arms, legs,glutei" Proximal stiff "E,A" Rigid N N c.1580G>C +EMD4 III-8 12 P15Y Minimal wasting Slowly progressive Y ++ 14 "Upper arms, legs,glutei" Proximal N "E,A" Rigid N na c.1580G>C +Spo28 36 P2Y "Fatigue, multiple sclerosis since 18y" Slowly progressive YD ++ 5 "Diffuse wasting, preddistal" "Proximal,Distal" "Proximal,Distal" Hyperext "E,A,H" "Rigid, hyperext lordosis" Arrhythmia na c.1583C>A +Spo29 17 P1Y "Delayed motor development, fatigue" Slowly progressive Y ++ 5 "upper arm, upper leg, bilateral pes equinus" Mildly proximal "Proximal,Distal" stiff "E,A" Rigid Arrhythmia N c.1583C>A \ No newline at end of file