Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome.
Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome.
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DOI：
10.1038/s41436-020-01078-6
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Hanna N
中科院分区：
文献类型：
--
作者：
Arnaud P;Morel H;Milleron O;Gouya L;Francannet C;Da Costa A;Le Goff C;Jondeau G;Boileau C;Hanna N
在FBN 1基因中具有嵌合致病性变体的个体主要在家族筛查过程中描述。在文献中，几乎所有这些镶嵌个体都是无症状的。在这项研究中，我们报告了我们团队对5,000多名马凡氏综合征（MFS）先证者的经验。下一代测序（NGS）捕获技术使我们能够识别5例MFS先证者，他们在FBN 1基因中携带嵌合致病性变体。这5例散发性嵌合体先证者表现出马凡氏综合征常见的典型特征。结合文献结果，这些罕见的发现涉及单核苷酸变异和拷贝数变异。在MFS患者的分子诊断中，不应忽视这一被低估的发现，并需要对生物信息学分析中使用的参数进行调整。目前5例有症状的MFS先证者携带嵌合体FBN 1致病性变异，这强化了一个事实，即显然无症状的嵌合体父母应该进行完整的临床检查和定期的心血管随访。我们建议，对于未发现单核苷酸致病性变异或外显子缺失/重复的典型MFS患者，应使用NGS捕获面板和适应性变异调用分析进行检测。
Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.
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影响因子：
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作者：
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通讯作者：
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