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首页> 外文期刊>Neuromuscular disorders: NMD >Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy
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Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy

机译：深度测序可在未受影响的兄弟姐妹患有肾病性肌病的母亲中检测到极低度的体细胞镶嵌病

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摘要

When an expected mutation in a particular disease-causing gene is not identified in a suspected carrier, it is usually assumed to be due to germline mosaicism. We report here very-low-grade somatic mosaicism in ACTA1 in an unaffected mother of two siblings affected with a neonatal form of nemaline myopathy. The mosaicism was detected by deep resequencing using a next-generation sequencer. We identified a novel heterozygous mutation in ACTA1, c.448A>G (p.Thr150Ala), in the affected siblings. Three-dimensional structural modeling suggested that this mutation may affect polymerization and/or actin's interactions with other proteins. In this family, we expected autosomal dominant inheritance with either parent demonstrating germline or somatic mosaicism. Sanger sequencing identified no mutation. However, further deep resequencing of this mutation on a next-generation sequencer identified very-low-grade somatic mosaicism in the mother: 0.4%, 1.1%, and 8.3% in the saliva, blood leukocytes, and nails, respectively. Our study demonstrates the possibility of very-low-grade somatic mosaicism in suspected carriers, rather than germline mosaicism.
机译：当在可疑携带者中未鉴定出特定致病基因的预期突变时，通常认为这是由于种系镶嵌所致。我们在这里报道了ACTA1中非常低等的体细胞镶嵌病，这是一个未受影响的两个兄弟姐妹的母亲，其母亲受到新生儿形式的奈玛琳肌病的影响。通过使用下一代定序器进行深度重测序，可以检测到嵌合现象。我们在受影响的兄弟姐妹中的ACTA1，c.448A> G（p.Thr150Ala）中发现了一个新的杂合突变。三维结构建模表明该突变可能影响聚合和/或肌动蛋白与其他蛋白质的相互作用。在这个家族中，我们期望父母证明种系或体细胞镶嵌的常染色体显性遗传。 Sanger测序未发现突变。但是，在下一代测序仪上对该突变进行进一步的深度重测序后，发现母亲体内的体细胞镶嵌性非常低：唾液，血液白细胞和指甲中的体细胞镶嵌率分别为0.4％，1.1％和8.3％。我们的研究表明，在可疑携带者中存在极低度的体细胞镶嵌性而不是种系镶嵌性的可能性。

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