Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
By G. Carvill, S. Heavin, S. Yendle, J. Mcmahon, Brian J. O'Roak, Joseph Cook, Adiba Khan, M. Dorschner, M. Weaver, S. Calvert and 24 more. Nature Genetics, 2013
657 citations recorded by the source corpus.
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
Subfields: Genetics, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/0011c4e04a2d743cd040482b5da65d3f640380de
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In Genetics
Citations in the corpus
- hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023, background): “Similarly, rare loss-of-function mutations have been reported in the SCN2A gene, a hub gene of the INH-M11 module.44 We also find enrichment of several ASD-associated genes such as TSC1 (INH-M8), SMARCA4 (INH-M8), SHANK2 (INH-M4), and CPEB4 (INH-M1), highlighting that these modules are functional an”
- The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity (2015, positive): “The list also includes recently implicated genes: CHD2 [35], CHD8 [36], KMT2E [37], MBD5 [35], SETD5 [38], and WDFY3 [39].”