杜氏肌营养不良症(DMD)和贝克尔肌营养不良症(BMD)是最常见的遗传性神经肌肉疾病。在先证者的DMD基因中鉴定出致病性致病变异后,潜在的携带者可以被告知他们有患病后代的风险。种系镶嵌是一种限于性腺的变体,可以传播给后代,通常在DMD致病性变体的非携带者有两个或多个携带该变体的后代时报告。平均而言,三分之一的病例是从头变异的结果,由于DMD和BMD容易发生种系镶嵌,将其纳入遗传咨询是强制性的。在这项回顾性队列研究中,我们提供了一项由332个家庭组成的未发表的DMD/BMD队列的临床数据,在从头传播为8.1%的家庭中,种系镶嵌症的发生率为8.1%.这也是第一个系统的文献综述搜索PubMed,以提供对DMD和BMD中种系镶嵌的当前文献的准确评估,包括17例病例报告和20项原始研究。从头事件家族中记录的种系镶嵌的发生率为6.0%至40%,均值为8.3%。具有经证实的从头因果变异的患者的母亲的估计复发风险范围为4.3%至11%,男性胎儿的平均值为5.8%。通过提供最新和全面的文献概述,这篇综述旨在提高我们对DMD中种系镶嵌性的认识,并促进在从头事件家族遗传咨询中制定有效的策略和可靠的发生风险评估数据.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most common inherited neuromuscular diseases. Following the identification of a pathogenic causative variant in the DMD gene of a proband, potential carriers can be informed of their risk of having offspring with the disease. Germline mosaicism is a variant that is confined to the gonads that can be transmitted to offspring and is usually reported when a non-carrier of a DMD pathogenic variant has two or more offspring carrying the variant in question. On average, one third of cases are the result of a de novo variant, and as DMD and BMD are prone to germline mosaicism, its inclusion in genetic counseling is mandatory. In this retrospective cohort
study, we presented clinical data from an unpublished DMD/BMD cohort of 332 families with incidence of germline mosaicism in families with de novo transmission of 8.1%. This is also the first systematic literature review searching PubMed to provide an accurate assessment of the current literature on germline mosaicism in DMD and BMD, including 17 case reports and 20 original studies. The incidence of documented germline mosaicism in de novo event families ranged from 6.0 to 40%, with a mean of 8.3%. The estimated recurrence risk for mothers of a patient with a proven de novo causal variant ranged from 4.3 to 11%, with a mean of 5.8% for a male fetus. By providing an up-to-date and comprehensive overview of the literature, this review aims to improve our understanding of germline mosaicism in DMD and to promote the development of effective strategies and reliable data for occurrence risk assessment in genetic counseling of de novo event families.