NOTCH1：其在淋巴管发育中的作用综述及对七个携带罕见致病性变异家族的研究。
NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants.
机构信息
Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy.
Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy.
出版信息
Mol Genet Genomic Med. 2021 Jan;9(1):e1529. doi: 10.1002/mgg3.1529. Epub 2020 Nov 28.
BACKGROUND
We developed a Next-Generation-Sequencing (NGS) protocol to screen the most frequent genetic variants related to lymphedema and a group of candidate genes. The aim of the study was to find the genetic cause of lymphedema in the analyzed patients.
METHODS
We sequenced a cohort of 246 Italian patients with lymphatic malformations. In the first step, we analyzed genes known to be linked to lymphedema: 235 out of 246 patients tested negative for the most frequent variants and underwent testing for variants in a group of candidate genes, including the NOTCH1 gene, selected from the database of mouse models. We also performed in silico analysis to observe molecular interactions between the wild-type and the variant amino acids and other protein residues.
RESULTS
Seven out of 235 probands, five with sporadic and two with familial lymphedema, were found to carry rare missense variants in the NOTCH1 gene.
CONCLUSIONS
Our results propose that NOTCH1 could be a novel candidate for genetic predisposition to lymphedema.
背景
我们开发了一种下一代测序（NGS）方案，以筛选与淋巴水肿相关的最常见遗传变异和一组候选基因。本研究的目的是在分析的患者中找到淋巴水肿的遗传原因。
方法
我们对 246 名意大利淋巴畸形患者进行了测序。在第一步中，我们分析了已知与淋巴水肿相关的基因：246 名患者中有 235 名未检测到最常见变异的患者，并对一组候选基因（包括从鼠模型数据库中选择的 NOTCH1 基因）进行了变异检测。我们还进行了计算机分析，以观察野生型和变异型氨基酸以及其他蛋白质残基之间的分子相互作用。
结果
235 名先证者中有 7 名，5 名散发性淋巴水肿和 2 名家族性淋巴水肿，携带 NOTCH1 基因的罕见错义变异。
结论
我们的结果表明 NOTCH1 可能是淋巴水肿遗传易感性的一个新候选基因。
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