Grossi Alice, Morelli Federico, Di Duca Marco, Caroli Francesco, Moroni Isabella, Tonduti Davide, Bachetti Tiziana, Ceccherini Isabella
UOSD Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Front Genet. 2021 Dec 7;12:744068. doi: 10.3389/fgene.2021.744068. eCollection 2021.
Alexander disease is a leukodystrophy caused by heterozygous mutations of 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 locus was performed with deep coverage (≥500×) in 11 probands and their parents (trios) with probands heterozygous for apparently 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.
亚历山大病是一种由基因杂合突变引起的脑白质营养不良。健康父母的子女出现复发情况，证实了变异通过生殖系嵌合现象进行传递。利用从外周血中分离出的DNA，对11名先证者及其父母（三联体）进行了基因座的下一代测序（NGS），测序深度≥500×，这些先证者对于明显的突变呈杂合状态。实际上，向患病同胞传递突变等位基因的一方父母存在体细胞嵌合现象，估计范围为8.9%-16%。父母的生殖系嵌合现象值得关注，因为它对于评估亚历山大病家庭的复发风险至关重要。
