Parental mosaicism for apparent de novo genetic variants: Scope, detection, and counseling challenges.
Parental mosaicism for apparent de novo genetic variants: Scope, detection, and counseling challenges.
复制标题
父母的摩西主义明显的从头遗传变异：范围，检测和咨询挑战。
作者：
新生突变（DNM）的疾病负担直到最近才得到证实，当时下一代测序技术的普遍应用使其能够通过基于家庭的临床外显子组或基因组测序进行可靠和负担得起的检测。将外显子组测序应用于产前诊断显示，高达63%的与胎儿结构异常相关的致病性或可能致病性变异显然是新生的，主要是常染色体显性遗传疾病。表观DNM被认为主要作为种系或合子事件发生，因此复发风险可忽略不计。然而，现在有证据表明，它们中的相当大一部分实际上是从变体的亲本嵌合体继承的。在这里，我们回顾了产前诊断中DNMs的负担和父母嵌合体对解释明显DNMs的影响，并讨论了检测和量化父母嵌合体及其对复发风险的影响所面临的挑战。我们还描述了新的生物信息学和技术工具，以评估镶嵌，并讨论他们如何提高生殖风险咨询的准确性时，检测到父母的镶嵌。
The disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next-generation sequencing technologies enabled their reliable and affordable detection through family-based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from a parent mosaic for the variant. Here, we review the burden of DNMs in prenatal diagnostics and the influence of parental mosaicism on the interpretation of apparent DNMs and discuss the challenges with detecting and quantifying parental mosaicism and its effect on recurrence risk. We also describe new bioinformatic and technological tools developed to assess mosaicism and discuss how they improve the accuracy of reproductive risk counseling when parental mosaicism is detected.
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影响因子：
12.3
作者：
Acuna-Hidalgo R;Veltman JA;Hoischen A
通讯作者：
Hoischen A
影响因子：
64.8
作者：
Coorens THH;Oliver TRW;Sanghvi R;Sovio U;Cook E;Vento-Tormo R;Haniffa M;Young MD;Rahbari R;Sebire N;Campbell PJ;Charnock-Jones DS;Smith GCS;Behjati S
通讯作者：
Behjati S
影响因子：
82.9
作者：
Breuss, Martin W.;Antaki, Danny;Gleeson, Joseph G.
通讯作者：
Gleeson, Joseph G.
影响因子：
46.9
作者：
Dou, Yanmei;Kwon, Minseok;Park, Peter J.
通讯作者：
Park, Peter J.
影响因子：
3.9
作者：
Bernkopf M;Hunt D;Koelling N;Morgan T;Collins AL;Fairhurst J;Robertson SP;Douglas AGL;Goriely A
通讯作者：
Goriely A