Yao Xiaoqian, Wu Jihong, Chen Junyi
Department of Ophthalmology & Visual Science and.
Experimental Research Center, Eye & ENT Hospital of Fudan University, Shanghai, China.
Ann Clin Lab Sci. 2019 Sep;49(4):539-545.
To detect the mutations in the fibronectin-1 gene () of four Chinese families with autosomal dominant Marfan syndrome (MFS), and to discuss the associated phenotypes.
We examined ten patients, and five non-carriers, in four Chinese families with autosomal dominant Marfan syndrome (MFS) for mutations. Comprehensive physical, ophthalmic, and cardiovascular examinations were performed on the family members. The gene was amplified with PCR from the DNA of the patients and their relatives. The amplified products were sequenced and compared with a reference sequence from the GenBank database. The changes in the structure and function of the protein caused by the amino acid substitution were investigated with a bioinformatics analysis.
In our study, sequencing revealed three novel mutations, and one mutation which was found earlier in 2012. One of the novel mutations is c.649T>C in exon 7, which results in the substitution tryptophan by arginine at codon 217 (p.Trp217Arg), the other is a splice defect in intron 39 (c.4816+1G>A), and the third one is c.407G>T in exon 5, which altered an amino acid at residue 136 from Cysteine to Phenylalanine (p.Cys136Phe). The recurrent mutation was c.4151T>C in exon 34, resulting in methionine being replaced by threonine (p.Met1384Thr). The occurrence of the mutations correlated strongly with the phenotypes of the patients, and no mutation was detected in the normal relatives of the affected patients.
In this study, three novel and a recurrent mutations were detected. The results expand the mutation spectrum of , helping in the study of molecular pathogenesis of MFS and Marfan-related disorders.
检测四个常染色体显性遗传马凡综合征（MFS）中国家系中纤连蛋白-1基因（ ）的突变情况，并探讨相关表型。
我们对四个常染色体显性遗传马凡综合征（MFS）中国家系中的10例患者及5名非携带者进行了 突变检测。对家系成员进行了全面的体格、眼科及心血管检查。采用聚合酶链反应（PCR）从患者及其亲属的DNA中扩增 基因。对扩增产物进行测序，并与GenBank数据库中的参考序列进行比较。通过生物信息学分析研究氨基酸替换导致的蛋白质结构和功能变化。
在本研究中，测序发现了三个新突变以及一个在2012年较早发现的突变。其中一个新突变是外显子7中的c.649T>C，导致密码子217处的色氨酸被精氨酸取代（p.Trp217Arg）；另一个是内含子39中的剪接缺陷（c.4816+1G>A）；第三个是外显子5中的c.407G>T，导致第136位氨基酸由半胱氨酸变为苯丙氨酸（p.Cys1 – 36Phe）。复发性突变是外显子34中的c.4151T>C，导致甲硫氨酸被苏氨酸取代（p.Met1384Thr）。这些突变的发生与患者的表型密切相关，在受累患者的正常亲属中未检测到突变。
本研究检测到三个新的和一个复发性 突变。研究结果扩展了 的突变谱，有助于马凡综合征及马凡相关疾病分子发病机制的研究。
