Identification of Novel FBN1 and TGFBR2 Mutations in 65 Probands With Marfan Syndrome or Marfan-Like Phenotypes
Identification of Novel FBN1 and TGFBR2 Mutations in 65 Probands With Marfan Syndrome or Marfan-Like Phenotypes
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DOI：
10.1002/ajmg.a.32918
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Lau, Yu-Lung
中科院分区：
文献类型：
--
作者：
Chung, Brian Hon-Yin;Lam, Stephen Tak-Sum;Lau, Yu-Lung
马凡氏综合征是一种常染色体显性遗传性结缔组织疾病，在MFS和相关表型的先证者中已发现FBN 1和TGFBR 2基因突变。采用DHPLC和测序技术，对65例马凡氏综合征及其相关表型的先证者的基因突变谱进行了研究。在FBN 1中总共鉴定了24个突变，其中19个（9个错义，6个移码，2个无义和2个影响剪接点）是新的。在剩下的41个先证者中，6个被鉴定为具有新的TGFBR 2突变（1个移码突变和5个错义突变）。本研究中发现的所有新突变均被证实在50名相同种族背景的无关正常个体中不存在。在符合根特标准的先证者（n = 16）中，81%的病例发现FBN 1突变。TGFBR 2突变的患者均不符合根特标准。根据最新的ACMG指南对意义未知的新型错义突变进行分类，并评估其致病的可能性。(C)2009 Wiley-Liss，Inc.
Marfan syndrome is an autosomal dominant connective tissue disorder, and mutations in the FBN1 and TGFBR2 genes have been identified in probands with MFS and related phenotypes. Using DHPLC and sequencing, we studied the mutation spectrum in 65 probands with Marfan syndrome and related phenotypes. A total of 24 mutations in FBN1 were identified, of which 19 (nine missense, six frameshift, two nonsense and two affecting splice junctions) were novel. In the remaining 41 probands, six were identified to have novel TGFBR2 mutations (one frameshift and five missense mutations). All novel mutations found in this study were confirmed to be absent in 50 unrelated normal individuals of the same ethnic background. In probands who fulfilled the Ghent criteria (n = 16), mutations in FBN1 were found in 81% of cases. None of those with TGFBR2 mutations fulfilled the Ghent criteria. Novel missense mutations of unknown significance were classified according to the latest ACMG guidelines and their likelihood to be causative was evaluated. (C) 2009 Wiley-Liss, Inc.