汉族FBN1基因突变所致马凡综合征一家系心血管表现的性别差异

 目的 通过分析一汉族马凡综合征家系多名患病成员的心血管系统受累表现与原纤维蛋白-1（FBN1）基因突变位点，提高对马凡综合征临床表现性别差异的认识。方法 收集一马凡综合征家系成员的心血管系统受累资料。在知情同意基础上采集外周血，提取基因组DNA，PCR扩增FBN1基因全部65个外显子及外显子内含子交界区，产物纯化后行Sanger法测序。结果 该家系共13名患者，所有9名存活患者均携带有c.5431G>A (p.Glu1811Lys)突变，而家族中正常个体无此突变。9名男性中4例猝死，另4名存在升主动脉扩张，1名表现为扩张性心肌病；4名女性中因心力衰竭死亡1例，另3名存在严重二尖瓣病变而无升主动脉扩张。结论 FBN1突变所致马凡综合征心血管系统受累即使是在同一家系中亦可表现为显著的差异。

Gender differences of cardiovascular involvement in a Han population family with Marfan Syndrome caused by FBN1 mutation

Objective To recognize the gender differences in cardiovascular presentation of Marfan syndrome by investigating a Han family of fibrillin-1(FNB1) mutation. Methods Cardiovascular involvement of all family members were collected and analyzed. Peripheral blood samples were collected from the proband and his family members with informed consent. Genomic DNA was isolated from peripheral blood leukocytes. The full 65 coding exons and their relevant exon-intron boundaries of the FBN1 gene were amplified using primers designed according to the published sequence of FBN1. After purification, the PCR products were subjected to automatic DNA sequencing. Results 13 patients were identified. All affected individuals carried mutation of c.5431G>A (p.Glu1811Lys)in FBN1, however, normal members had no mutation. Four male patients suffered from sudden death, one has dilated cardiomyopathy and the other 4 males have ascending aorta (AA) dilation. One female patient died of heart failure and the other three females have severe mitral valve regurgitation without AA dilation. Conclusions Significant gender differences on cardiovascular presentation may exist even in one family of Marfan syndrome with the same FBN1 mutation.