학술논문
Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation
Document Type
article
Author
Source
Frontiers in Genetics, Vol 12 (2021)
Subject
Language
English
ISSN
1664-8021
Abstract
Alexander disease is a leukodystrophy caused by heterozygous mutations of GFAP gene. Recurrence in siblings from healthy parents provides a confirmation to the transmission of variants through germinal mosaicism. With the use of DNA isolated from peripheral blood, next-generation sequencing (NGS) of GFAP locus was performed with deep coverage (≥500×) in 11 probands and their parents (trios) with probands heterozygous for apparently de novo GFAP mutations. Indeed, one parent had somatic mosaicism, estimated in the range of 8.9%–16%, for the mutant allele transmitted to the affected sibling. Parental germline mosaicism deserves attention, as it is critical in assessing the risk of recurrence in families with Alexander disease.