Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort.

ABSTRACT: Genomic mosaicism in parental gametes and peripheral tissues is an important consideration for genetic counseling. We studied a Chinese cohort affected by a severe epileptic disorder, Dravet syndrome (DS). There were 56 fathers who donated semen and 15 parents who donated multiple peripheral tissue samples. We used an ultra-sensitive quantification method, micro-droplet digital PCR (mDDPCR), to detect parental mosaicism of the proband's pathogenic mutation in SCN1A, the causal gene of DS in 112 families. Ten of the 56 paternal sperm samples were found to exhibit mosaicism of the proband's mutations, with mutant allelic fractions (MAFs) ranging from 0.03% to 39.04%. MAFs in the mosaic fathers' sperm were significantly higher than those in their blood (p?=?0.00098), even after conditional probability correction (p'?=?0.033). In three mosaic fathers, ultra-low fractions of mosaicism (MAF?

SUBMITTER: Yang X 

PROVIDER: S-EPMC5688122 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature