AUTHOR=Grossi Alice , Morelli Federico , Di Duca Marco , Caroli Francesco , Moroni Isabella , Tonduti Davide , Bachetti Tiziana , Ceccherini Isabella 

TITLE=Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation 

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.744068

DOI=10.3389/fgene.2021.744068

ISSN=1664-8021

ABSTRACT=Alexander disease is a leukodystrophy caused by heterozygous mutations of the GFAP gene. Recurrence in siblings from healthy parents provides a confirmation to the transmission of variants through germinal mosaicism. Using DNA isolated from peripheral blood, Next Generation Sequencing (NGS) of the GFAP locus was performed with deep coverage (≥500X) 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 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.