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 (>= 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 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.

Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation / A. Grossi, F. Morelli, M. Di Duca, F. Caroli, I. Moroni, D. Tonduti, T. Bachetti, I. Ceccherini. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 12:(2021), pp. 744068.1-744068.5. [10.3389/fgene.2021.744068]

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

D. Tonduti;
2021

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 (>= 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 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.
Alexander disease; DNA sequence analysis; GFAP gene; central nervous system diseases; genetic counseling; germline mosaicism; human genetics; somatic mosaicism
Settore MED/39 - Neuropsichiatria Infantile
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/938833
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