A FBN1 mutation association with different phenotypes of Marfan syndrome in a Chinese family
A FBN1 mutation association with different phenotypes of Marfan syndrome in a Chinese family
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DOI：
10.1016/j.cca.2016.06.031
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发表时间：
2016-09-01
影响因子：
5
通讯作者：
Zhang, Yanzhou
中科院分区：
文献类型：
--
作者：
Li, Yapeng;Xu, Jianhua;Zhang, Yanzhou
背景资料：先前的研究表明，与携带相同突变的相关家族的不同成员相比，具有不同FBN 1突变的患者通常呈现更大的表型变异。本研究的目的是在一个中国马凡氏综合征家系中发现致病突变，并提供更多关于基因型表型相关性的信息，方法：对一个四代马凡氏综合征家系的15名相关成员进行体格检查、眼科检查、放射学检查和心血管检查。先证者患有De Bakey III型主动脉夹层，不符合修订后的马凡氏综合征根特标准。9名家族成员有晶状体异位，超声心动图正常。其他五名家庭成员没有马凡氏综合征的证据。从血液白细胞中分离基因组DNA。结果：先证者FBN 1基因第14外显子（NM 000138）存在c.1633T>G（p.R545C）的杂合错义突变。在所有9例晶状体异位患者和1例未受影响的8岁女孩中也发现了相同的突变。结论：我们的数据增强了由于FBN 1突变的基因型-表型相关性的信息。据我们目前所知，我们首次报道了同一个家族中同时检测到三种不同的主要表型（晶状体异位、主动脉夹层和未受累）的FBN 1突变c.1633C>T（Arg 545 Cys）。FBN 1突变的未受影响的女孩可能代表了一种罕见的非遗传性病例。(C)2016爱思唯尔B. V.保留所有权利。
Background: Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype phenotypic correlations in a large Chinese family with Marfan syndrome.Methods: 15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family.Results: The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentis patients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members.Conclusions: Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c.1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance. (C) 2016 Elsevier B.V. All rights reserved.