Whole exome sequencing Gene package Epilepsy version 1,

Transcription

1 Whole Exome Sequencing Gene package Epilepsy, version 1, Technical information After DNA was enriched using Agilent Sureselect Clinical Research Exome (CRE) Capture, samples were run on the Illumina Hiseq platform. The aim is to obtain 50 million total reads per exome with a mapped fraction >0.98. The average coverage of the exome is ~50x. Data are demultiplexed by Illumina software bcl2fastq. Reads are mapped to the genome using BWA (reference: bwa.sourceforge.net/). Variant detection is performed by Genome Analysis Toolkit (reference: Analysis is performed in Cartagenia using The Variant Calling File (VCF) followed by filtering. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including phenotype ID(s) median depth ABAT GABA transaminase deficiency, ABCC8 Hyperinsulinemic hypoglycemia, familial, 1, Hypoglycemia of infancy, leucine sensitive, Diabetes mellitus, transient neonatal 2, Diabetes mellitus, noninsulin dependent, Diabetes mellitus, permanent neonatal, ACY1 Aminoacylase 1 deficiency, ADSL Adenylosuccinase deficiency, ALDH7A1 Epilepsy, pyridoxine dependent, ALG13 Epileptic encephalopathy, early infantile, 36, AMACR Alpha methylacyl CoA racemase deficiency, Bile acid synthesis defect, congenital, 4, AMT Glycine encephalopathy, ARHGEF9 Epileptic encephalopathy, early infantile, 8, ARX Epileptic encephalopathy, early infantile, 1, Lissencephaly, X linked 2, Mental retardation, X linked 29 and others, Proud syndrome, Partington syndrome, Hydranencephaly with abnormal genitalia,

2 Phenotype description including phenotype ID(s) median depth ASAH1 Farber lipogranulomatosis, Spinal muscular atrophy with progressive myoclonic epilepsy, ATP1A2 Migraine, familial hemiplegic, 2, Alternating hemiplegia of childhood, Migraine, familial basilar, ATP6AP2?Mental retardation, X linked, syndromic, Hedera type, ?Parkinsonism with spasticity, X linked, ATP7A Menkes disease, Occipital horn syndrome, Spinal muscular atrophy, distal, X linked 3, ATRX Alpha thalassemia/mental retardation syndrome, Alpha thalassemia myelodysplasia syndrome, somatic, Mental retardation hypotonic facies syndrome, X linked, BOLA3 Multiple mitochondrial dysfunctions syndrome 2, BTD Biotinidase deficiency, CACNA1A Migraine, familial hemiplegic, 1, Episodic ataxia, type 2, Spinocerebellar ataxia 6, Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, CASK Mental retardation and microcephaly with pontine and cerebellar hypoplasia, FG syndrome 4, Mental retardation, with or without nystagmus, CDKL5 Epileptic encephalopathy, early infantile, 2, CHD2 Epileptic encephalopathy, childhood onset, CHRNA2 Epilepsy, nocturnal frontal lobe, type 4, CHRNA4 Epilepsy, nocturnal frontal lobe, 1, {Nicotine addiction, susceptibility to}, CHRNB2 Epilepsy, nocturnal frontal lobe, 3, CLDN16 Hypomagnesemia 3, renal, CLDN19 Hypomagnesemia 5, renal, with ocular involvement, CLN3 Ceroid lipofuscinosis, neuronal, 3, CLN5 Ceroid lipofuscinosis, neuronal, 5, CLN6 Ceroid lipofuscinosis, neuronal, 6, Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, CLN8 Ceroid lipofuscinosis, neuronal, 8, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, CNNM2 Hypomagnesemia 6, renal, Hypomagnesemia, seizures, and mental retardation, CNTN2?Epilepsy, myoclonic, familial adult, 5,

3 Phenotype description including phenotype ID(s) median depth CNTNAP2 Cortical dysplasia focal epilepsy syndrome, {Autism susceptibility 15}, Pitt Hopkins like syndrome 1, COQ2 Coenzyme Q10 deficiency, primary, 1, {Multiple system atrophy, susceptibility to}, CPA6 Epilepsy, familial temporal lobe, 5, Febrile seizures, familial, 11, CPS1 Carbamoylphosphate synthetase I deficiency, {Pulmonary hypertension, neonatal, susceptibility to}, {Venoocclusive disease after bone marrow transplantation} CPT2 Myopathy due to CPT II deficiency, CPT deficiency, hepatic, type II, CPT II deficiency, lethal neonatal, {Encephalopathy, acute, infection induced, 4, susceptibility to}, CSTB Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), CTSD Ceroid lipofuscinosis, neuronal, 10, CTSF Ceroid lipofuscinosis, neuronal, 13, Kufs type, CUL4B Mental retardation, X linked, syndromic 15 (Cabezas type), D2HGDH D 2 hydroxyglutaric aciduria, DCX Lissencephaly, X linked, Subcortical laminal heteropia, X linked, DEPDC5 Epilepsy, familial focal, with variable foci, DLAT Pyruvate dehydrogenase E2 deficiency, DNAJC5 Ceroid lipofuscinosis, neuronal, 4, Parry type, DPYD Dihydropyrimidine dehydrogenase deficiency, fluorouracil toxicity, DYNC1H1 Charcot Marie Tooth disease, axonal, type 20, Mental retardation, autosomal dominant 13, Spinal muscular atrophy, lower extremity predominant 1, AD, DYRK1A Mental retardation, autosomal dominant 7, EEF1A2 Mental retardation, autosomal dominant 38, Epileptic encephalopathy, early infantile, 33, EGF Hypomagnesemia 4, renal, EHMT1 Kleefstra syndrome, EPM2A Epilepsy, progressive myoclonic 2A (Lafora), FARS2 Combined oxidative phosphorylation deficiency 14, FGD1 Aarskog Scott syndrome, Mental retardation, X linked syndromic 16,

4 Phenotype description including phenotype ID(s) median depth FLNA Heterotopia, periventricular, Otopalatodigital syndrome, type I, Otopalatodigital syndrome, type II, Intestinal pseudoobstruction, neuronal, Melnick Needles syndrome, Frontometaphyseal dysplasia, Heterotopia, periventricular, ED variant, FG syndrome 2, Cardiac valvular dysplasia, X linked, Terminal osseous dysplasia, Congenital short bowel syndrome, FOLR1 Neurodegeneration due to cerebral folate transport deficiency, FOXG1 Rett syndrome, congenital variant, FOXRED1 Leigh syndrome due to mitochondrial complex I deficiency, Mitochondrial complex I deficiency, FXYD2 Hypomagnesemia 2, renal, GABRA1 {Epilepsy, juvenile myoclonic, susceptibility to, 5}, {Epilepsy, childhood absence, susceptibility to, 4}, Epileptic encephalopathy, early infantile, 19, GABRG2 Epilepsy, generalized, with febrile seizures plus, type 3, {Epilepsy, childhood absence, susceptibility to, 2}, Febrile seizures, familial, 8, GAMT Cerebral creatine deficiency syndrome 2, GCK MODY, type II, Diabetes mellitus, noninsulin dependent, late onset, Hyperinsulinemic hypoglycemia, familial, 3, Diabetes mellitus, permanent neonatal, GCSH Glycine encephalopathy, GLDC Glycine encephalopathy, GLRA1 Hyperekplexia, hereditary 1, autosomal dominant or recessive, GLRB Hyperekplexia 2, autosomal recessive, GLUD1 Hyperinsulinism hyperammonemia syndrome, GNAO1 Epileptic encephalopathy, early infantile, 17, GPC3 Simpson Golabi Behmel syndrome, type 1, Wilms tumor, somatic, GPHN Molybdenum cofactor deficiency C, GRIA3 Mental retardation, X linked 94, GRIN1 Mental retardation, autosomal dominant 8, GRIN2A Epilepsy, focal, with speech disorder and with or without mental retardation,

5 Phenotype description including phenotype ID(s) median depth GRIN2B Mental retardation, autosomal dominant 6, Epileptic encephalopathy, early infantile, 27, GRN Frontotemporal lobar degeneration with ubiquitin positive inclusions, Aphasia, primary progressive, Ceroid lipofuscinosis, neuronal, 11, HADH 3 hydroxyacyl CoA dehydrogenase deficiency, Hyperinsulinemic hypoglycemia, familial, 4, HDAC4 No phenotype HLCS Holocarboxylase synthetase deficiency, HNRNPU No phenotype HSD17B10 17 beta hydroxysteroid dehydrogenase X deficiency, ?Mental retardation, X linked syndromic 10, HSD17B4 D bifunctional protein deficiency, Perrault syndrome 1, IDH2 D 2 hydroxyglutaric aciduria 2, IER3IP1 Microcephaly, epilepsy, and diabetes syndrome, IQSEC2 Mental retardation, X linked 1, KANSL1 Koolen De Vries syndrome, KCNA1 Episodic ataxia/myokymia syndrome, KCNJ10 SESAME syndrome, Enlarged vestibular aqueduct, digenic, KCNJ11 Hyperinsulinemic hypoglycemia, familial, 2, Diabetes, permanent neonatal, Diabetes mellitus, permanent neonatal, with neurologic features, {Diabetes mellitus, type 2, susceptibility to}, Diabetes mellitus, transient neonatal, 3, Maturity onset diabetes of the young, type 13, KCNMA1 Generalized epilepsy and paroxysmal dyskinesia, KCNQ2 Seizures, benign neonatal, 1, Myokymia, Epileptic encephalopathy, early infantile, 7, KCNQ3 Seizures, benign neonatal, type 2, KCNT1 Epileptic encephalopathy, early infantile, 14, Epilepsy, nocturnal frontal lobe, 5, KCTD7 Epilepsy, progressive myoclonic 3, with or without intracellular inclusions, KDM5C Mental retardation, X linked, syndromic, Claes Jensen type, LGI1 Epilepsy, familial temporal lobe, 1, LIAS Pyruvate dehydrogenase lipoic acid synthetase deficiency, MBD5 Mental retardation, autosomal dominant 1,

6 Phenotype description including phenotype ID(s) median depth MECP2 Rett syndrome, Mental retardation, X linked, syndromic 13, Rett syndrome, preserved speech variant, Encephalopathy, neonatal severe, {Autism susceptibility, X linked 3}, Mental retardation, X linked syndromic, Lubs type, Rett syndrome, atypical, MED12 Opitz Kaveggia syndrome, Lujan Fryns syndrome, Ohdo syndrome, X linked, MEF2C Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, Chromosome 5q14.3 deletion syndrome, MFSD8 Ceroid lipofuscinosis, neuronal, 7, Macular dystrophy with central cone involvement, MOCS1 Molybdenum cofactor deficiency A, MOCS2 Molybdenum cofactor deficiency B, MTHFR Homocystinuria due to MTHFR deficiency, {Schizophrenia, susceptibility to}, {Vascular disease, susceptibility to} {Neural tube defects, susceptibility to}, {Thromboembolism, susceptibility to}, MTOR Smith Kingsmore syndrome, NDUFA1 Mitochondrial complex I deficiency, NDUFA11 Mitochondrial complex I deficiency, NDUFAF1 Mitochondrial complex I deficiency, NDUFAF2 Mitochondrial complex I deficiency, Leigh syndrome, NDUFAF3 Mitochondrial complex I deficiency, NDUFAF4 Mitochondrial complex I deficiency, NDUFAF5 Mitochondrial complex 1 deficiency, NDUFB3 Mitochondrial complex I deficiency, NDUFB9?Mitochondrial complex I deficiency, NDUFS1 Mitochondrial complex I deficiency, NDUFS2 Mitochondrial complex I deficiency, NDUFS3 Leigh syndrome due to mitochondrial complex I deficiency, Mitochondrial complex I deficiency, NDUFS4 Leigh syndrome, Mitochondrial complex I deficiency, NDUFS6 Mitochondrial complex I deficiency,

7 Phenotype description including phenotype ID(s) median depth NDUFV1 Mitochondrial complex I deficiency, NDUFV2 Mitochondrial complex I deficiency, NECAP1?Epileptic encephalopathy, early infantile, 21, NEDD4L No phenotype NHLRC1 Epilepsy, progressive myoclonic 2B (Lafora), NRXN1 Pitt Hopkins like syndrome 2, {Schizophrenia, susceptibility to, 17}, NUBPL Mitochondrial complex I deficiency, OFD1 Orofaciodigital syndrome I, Simpson Golabi Behmel syndrome, type 2, Joubert syndrome 10, ?Retinitis pigmentosa 23, OPHN1 Mental retardation, X linked, with cerebellar hypoplasia and distinctive facial appearance, PAK3 Mental retardation, X linked 30/47, PC Pyruvate carboxylase deficiency, PCDH19 Epileptic encephalopathy, early infantile, 9, PDHA1 Pyruvate dehydrogenase E1 alpha deficiency, PDHB Pyruvate dehydrogenase E1 beta deficiency, PDP1 Pyruvate dehydrogenase phosphatase deficiency, PEX1 Peroxisome biogenesis disorder 1A (Zellweger), Peroxisome biogenesis disorder 1B (NALD/IRD), Heimler syndrome 1, PEX10 Peroxisome biogenesis disorder 6A (Zellweger), Peroxisome biogenesis disorder 6B, PEX12 Peroxisome biogenesis disorder 3A (Zellweger), Peroxisome biogenesis disorder 3B, PEX13 Peroxisome biogenesis disorder 11A (Zellweger), Peroxisome biogenesis disorder 11B, PEX14 Peroxisome biogenesis disorder 13A (Zellweger), PEX16 Peroxisome biogenesis disorder 8A, (Zellweger), Peroxisome biogenesis disorder 8B, PEX19 Peroxisome biogenesis disorder 12A (Zellweger), PEX26 Peroxisome biogenesis disorder 7A (Zellweger), Peroxisome biogenesis disorder 7B, PEX3 Peroxisome biogenesis disorder 10A (Zellweger), PEX5 Peroxisome biogenesis disorder 2A (Zellweger), Peroxisome biogenesis disorder 2B, Rhizomelic chondrodysplasia punctata, type 5,

8 Phenotype description including phenotype ID(s) median depth PEX6 Peroxisome biogenesis disorder 4A (Zellweger), Peroxisome biogenesis disorder 4B, Heimler syndrome 2, PHF6 Borjeson Forssman Lehmann syndrome, PHGDH Phosphoglycerate dehydrogenase deficiency, Neu Laxova syndrome 1, PIGA Paroxysmal nocturnal hemoglobinuria, somatic, Multiple congenital anomalies hypotonia seizures syndrome 2, PIGN Multiple congenital anomalies hypotonia seizures syndrome 1, PIGO Hyperphosphatasia with mental retardation syndrome 2, PLA2G6 Infantile neuroaxonal dystrophy 1, Neurodegeneration with brain iron accumulation 2B, Parkinson disease 14, autosomal recessive, PLCB1 Epileptic encephalopathy, early infantile, 12, PLP1 Pelizaeus Merzbacher disease, Spastic paraplegia 2, X linked, PNKP Microcephaly, seizures, and developmental delay, Ataxia oculomotor apraxia 4, PNPO Pyridoxamine 5' phosphate oxidase deficiency, POLG Progressive external ophthalmoplegia, autosomal recessive 1, Progressive external ophthalmoplegia, autosomal dominant 1, Mitochondrial DNA depletion syndrome 4B (MNGIE type), Mitochondrial DNA depletion syndrome 4A (Alpers type), Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), PPT1 Ceroid lipofuscinosis, neuronal, 1, PQBP1 Renpenning syndrome, PRICKLE1 Epilepsy, progressive myoclonic 1B, PRRT2 Episodic kinesigenic dyskinesia 1, Seizures, benign familial infantile, 2, Convulsions, familial infantile, with paroxysmal choreoathetosis, RAB39B Mental retardation, X linked 72, ?Waisman syndrome, RARS2 Pontocerebellar hypoplasia, type 6, RNASEH2A Aicardi Goutieres syndrome 4, RNASEH2B Aicardi Goutieres syndrome 2, RNASEH2C Aicardi Goutieres syndrome 3, ROGDI Kohlschutter Tonz syndrome, RPS6KA3 Coffin Lowry syndrome, Mental retardation, X linked 19,

9 Phenotype description including phenotype ID(s) RRM2B Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, Mitochondrial DNA depletion syndrome 8B (MNGIE type), median depth SAMHD1 Aicardi Goutieres syndrome 5, ?Chilblain lupus 2, SCARB2 Epilepsy, progressive myoclonic 4, with or without renal failure, SCN1A Epilepsy, generalized, with febrile seizures plus, type 2, Dravet syndrome, Migraine, familial hemiplegic, 3, Febrile seizures, familial, 3A, SCN1B Epilepsy, generalized, with febrile seizures plus, type 1, Brugada syndrome 5, Cardiac conduction defect, nonspecific, Atrial fibrillation, familial, 13, SCN2A Seizures, benign familial infantile, 3, Epileptic encephalopathy, early infantile, 11, SCN8A?Cognitive impairment with or without cerebellar ataxia, Epileptic encephalopathy, early infantile, 13, SCN9A Erythermalgia, primary, Paroxysmal extreme pain disorder, , Insensitivity to pain, congenital, Febrile seizures, familial, 3B, Epilepsy, generalized, with febrile seizures plus, type 7, Small fiber neuropathy, {Dravet syndrome, modifier of}, HSAN2D, autosomal recessive, SLC16A1 Erythrocyte lactate transporter defect, Hyperinsulinemic hypoglycemia, familial, 7, Monocarboxylate transporter 1 deficiency, SLC19A3 Thiamine metabolism dysfunction syndrome 2 (biotin or thiamine responsive encephalopathy type 2), SLC25A1 Combined D 2 and L 2 hydroxyglutaric aciduria, SLC25A15 Hyperornithinemia hyperammonemia homocitrullinemia syndrome, SLC25A22 Epileptic encephalopathy, early infantile, 3,

10 Phenotype description including phenotype ID(s) median depth SLC2A1 GLUT1 deficiency syndrome 1, infantile onset, severe, GLUT1 deficiency syndrome 2, childhood onset, {Epilepsy, idiopathic generalized, susceptibility to, 12}, Dystonia 9, Stomatin deficient cryohydrocytosis with neurologic defects, SLC35A2 Congenital disorder of glycosylation, type IIm, SLC6A8 Cerebral creatine deficiency syndrome 1, SLC9A6 Mental retardation, X linked syndromic, Christianson type, SMS Mental retardation, X linked, Snyder Robinson type, SPTAN1 Epileptic encephalopathy, early infantile, 5, SRPX2?Rolandic epilepsy, mental retardation, and speech dyspraxia, ST3GAL3 Mental retardation, autosomal recessive 12, Epileptic encephalopathy, early infantile, 15, STXBP1 Epileptic encephalopathy, early infantile, 4, SUOX Sulfite oxidase deficiency, SYN1 Epilepsy, X linked, with variable learning disabilities and behavior disorders, SYNGAP1 Mental retardation, autosomal dominant 5, SYP Mental retardation, X linked 96, SZT2 Epileptic encephalopathy, early infantile, 18, TBC1D24 Myoclonic epilepsy, infantile, familial, Epileptic encephalopathy, early infantile, 16, DOOR syndrome, Deafness, autosomal recessive 86, Deafness, autosomal dominant 65, TBCE Kenny Caffey syndrome, type 1, Hypoparathyroidism retardation dysmorphism syndrome, TCF4 Pitt Hopkins syndrome, Corneal dystrophy, Fuchs endothelial, 3, TDP2 No phenotype TPP1 Ceroid lipofuscinosis, neuronal, 2, Spinocerebellar ataxia, autosomal recessive 7, TREX1 Aicardi Goutieres syndrome 1, dominant and recessive, Chilblain lupus, Vasculopathy, retinal, with cerebral leukodystrophy, {Systemic lupus erythematosus, susceptibility to}, TRPM6 Hypomagnesemia 1, intestinal, UBE3A Angelman syndrome, ZEB2 Mowat Wilson syndrome, Gene symbols according HGCN

11 Phenotype description including phenotype ID(s) Gene symbols according HGCN release used: "No phenotypes" indicates a gene without a current association phenotypes between "[ ]", indicate "nondiseases," mainly genetic variations that lead to apparently abnormal laboratory test values phenotypes between "{}", indicate risk factors phenotypes with a question mark, "?", before the disease name indicates an unconfirmed or possibly spurious mapping. The statistics above are based on a set of 50 samples Median depth is the median of the mean sequence depth over the protein coding exons of the transcript % Covered 10x describes the percentage of a gene s coding sequence that is covered at least 10x % Covered 20x describes the percentage of a gene s coding sequence that is covered at least 20x median depth