Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome.
Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome.
复制标题
新一代测序鉴定出两个中国马凡氏综合征家族的 FBN1 基因新突变
DOI：
10.3892/mmr.2016.5229
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Wei X
中科院分区：
文献类型：
--
作者：
Ma M;Li Z;Wang DW;Wei X
马凡氏综合征（MFS）是一种常染色体显性遗传异质性结缔组织疾病，其特征是胸部动脉瘤/夹层的早期发展，以及眼部和骨骼系统的缺陷。由基因FBN 1（MFS-1）编码的转录因子蛋白-1（FBN 1）和转化生长因子β受体2（TGFBR 2）基因TGFBR 2（MFS-2）中的功能丧失突变是这种疾病的主要原因。本研究描述了一种快速、经济的MFS基因诊断方法，并用于鉴定中国大陆两个无亲缘关系的MFS家系的致病突变。使用靶向半导体测序，在两个家系的4名MFS患者中鉴定出两个致病突变，包括FBN 1基因中的新移码插入p.G2120fsX2160和报告的无义突变p.Arg529X（rs 137854476）。此外，一种罕见的，可能是良性的中国特有的FBN 1基因的多态性也被发现。
Marfan syndrome (MFS) is an autosomal dominant heterogeneous disorder of connective tissue characterized by the early development of thoracic aneurysms/dissections, together with defects of the ocular and skeletal systems. Loss-of-function mutations in fibrillin-1 (FBN1) encoded by the gene, FBN1 (MFS-1), and in the transforming growth factor β receptor 2 (TGFBR2) gene, TGFBR2 (MFS-2), are major causes of this disorder. In the present study, a rapid and cost-effective method for genetically diagnosing MFS was described and used to identify disease-causing mutations in two unrelated pedigrees with MFS in mainland China. Using targeted semiconductor sequencing, two pathogenic mutations in four MFS patients of the two pedigrees were identified, including a novel frameshift insertion, p.G2120fsX2160, and a reported nonsense mutation, p.Arg529X (rs 137854476), in the FBN1 gene. In addition, a rare, probably benign Chinese-specific polymorphism in the FBN1 gene was also revealed.