Zhao Liming, Liang Ting, Xu Jianzhen, Lin Hui, Li Dandan, Qi Yanhua
Department of Ophthalmology, Harbin Medical University, the 2nd Affiliated Hospital, Harbin, China.
Mol Vis. 2009;15:826-32. Epub 2009 Apr 23.
To identify the molecular defects in the fibrillin-1 gene (FBN1) in two Chinese families with ectopia lentis (EL) and marfanoid habitus.
Five patients and eight non-carriers in the two families underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the families as well as 100 healthy normal controls. Polymerase chain reaction (PCR) amplification and direct sequencing of all 65 coding exons of FBN1 were analyzed. The functional consequences of the mutations were analyzed with various genomic resources.
Two novel mutations of FBN1 were identified in our study. One is a splice defect in intron 17 (IVS 17-1G>T) adjacent to exon 18. The other is c.6182G>T in exon 50, which results in the substitution of cysteine by phenylalanine at codon 2,061 (p. C2061F). We provided strong evidences that the splice mutation would potentially lead to the skipping of exons after intron 17 and that the missense mutation at codon 2,061 (p. C2061F) would destroy a disulfide bond.
We detected two novel mutations in FBN1. Our results expand the mutation spectrum of FBN1 and help in the study of the molecular pathogenesis of Marfan syndrome and Marfan-related disorders.
鉴定两个患有晶状体异位（EL）和类马凡体型的中国家系中纤连蛋白-1基因（FBN1）的分子缺陷。
两个家系中的5例患者和8名非携带者接受了全面的体格、眼科和心血管检查。从这些家系个体以及100名健康正常对照者的静脉血白细胞中提取基因组DNA。对FBN1的所有65个编码外显子进行聚合酶链反应（PCR）扩增和直接测序分析。利用各种基因组资源分析突变的功能后果。
本研究鉴定出FBN1的两个新突变。一个是与外显子18相邻的内含子17中的剪接缺陷（IVS 17-1G>T）。另一个是外显子50中的c.6182G>T，导致密码子2061处的半胱氨酸被苯丙氨酸取代（p.C2061F）。我们提供了有力证据，表明剪接突变可能导致内含子17之后的外显子跳跃，并且密码子2061处的错义突变（p.C2061F）会破坏一个二硫键。
我们在FBN1中检测到两个新突变。我们的结果扩展了FBN1的突变谱，有助于研究马凡综合征和马凡相关疾病的分子发病机制。
