Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort

The contribution and genetic spectrum of de novo mutations (DNMs) was confirmed in infantile spasms (ISs). Somatic mutation accounted for 22.7% of DNMs in IS patients. Treatment with levetiracetam improved the prognosis of STXBP1-related ISs. AbstractObjectiveWe determined the yield, genetic spectrum, and actual origin of de novo mutations (DNMs) for infantile spasms (ISs) in a Chinese cohort. The efficacy of levetiracetam (LEV) forSTXBP1-related ISs was explored also.MethodsTargeted sequencing of 153 epilepsy-related candidate genes was applied to 289 Chinese patients with undiagnosed ISs. Trio-based amplicon deep sequencing was used for all DNMs to distinguish somatic/mosaic mutations from germline ones.ResultsTotal of 26 DNMs were identified from 289 recruited Chinese patients with undiagnosed ISs. Among them, 24 DNMs were interpreted as pathogenic mutations based on American College of Medical Genetics and Genomics guidelines, contributing to 8.3% (24/289) of diagnosis yield in the Chinese IS cohort.CDKL5 andSTXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. Further deep resequencing for the trio members showed that 22.7% (5/22) of DNMs are actually somatic in the proband or a parent. These somatic carriers presented milder seizure attacks than those with true germline DNMs. After treatment with LEV for half a year, three patients with DNM inSTXBP1 showed improved clinical symptoms, including seizure-free and normal electroencephalogram, e...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research