To further assess the scale and level of parental somatic mosaicism, we queried the CMA database at Baylor Genetics. We selected 50 unrelated families where clinically relevant apparent de novo CNV-deletions were found in the affected probands. Parental blood samples screening using deletion junction-specific PCR revealed four parents with somatic mosaicism. Droplet digital PCR (ddPCR), qPCR, and amplicon-based next-generation sequencing (NGS) were used. Using ddPCR levels of mosaicism ranged from undetectable to 18.5%. Amplicon-based NGS and qPCR for the father with undetectable mosaicism was able to detect mosaicism at 0.39%. In one mother, ddPCR analysis revealed 15.6%, 10.6%, 8.2%, and undetectable levels of mosaicism in her blood, buccal cells, saliva, and urine samples, respectively. Our data suggest that more sensitive and precise methods, e.g. CNV junction-specific LR-PCR, ddPCR, or qPCR may allow for a more refined assessment of the potential disease recurrence risk for an identified variant.

中文翻译：

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CNV 缺失的亲本体细胞嵌合 - 在临床诊断环境中需要更灵敏和更精确的检测方法。

为了进一步评估父母体细胞嵌合的规模和水平，我们查询了 Baylor Genetics 的 CMA 数据库。我们选择了 50 个不相关的家族，其中在受影响的先证者中发现了临床相关的明显新发 CNV 缺失。使用缺失连接特异性 PCR 筛选亲本血液样本显示四位亲本具有体细胞嵌合体。使用了液滴数字 PCR (ddPCR)、qPCR 和基于扩增子的下一代测序 (NGS)。使用 ddPCR 的嵌合水平范围从无法检测到 18.5%。对于无法检测到嵌合体的父亲，基于扩增子的 NGS 和 qPCR 能够检测到 0.39% 的嵌合体。在一位母亲中，ddPCR 分析显示她的血液、口腔细胞、唾液和尿液样本中分别有 15.6%、10.6%、8.2% 和无法检测到的嵌合体水平。我们的数据表明，更灵敏、更精确的方法，