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=12 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 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.