FBN1基因新突变导致常染色体显性遗传眼病晶状体脱位一家系三例分析

目的 通过对一汉族晶状体脱位家系3名患病成员的原纤维蛋白-1（FBN1）基因突变分析，追踪观察眼睛、心血管及全身临床表现，分析FBN1基因突变与临床表型关系。方法 系列病例研究。收集该家系所有成员的眼与心血管系统等全身临床资料。采用聚合酶链式反应和直接测序法对该家系所有成员进行FBN1基因的突变检测。结果 研究发现3名晶状体脱位患者均携带FBN1基因一个新的错义突变（c.1999T>C；p.Cys 515Arg），而家系中正常个体无此变异。SIFT和PolyPhen-2生物信息学分析数据高度支持该变异为致病性突变。家系中3名患者均存在不同程度的晶状体脱位，1名年长患者还伴有主动脉瘤样扩张。结论 FBN1基因c.1999T>C的突变可导致常染色体显性遗传眼病晶状体脱位。家系患者的的临床表现存在异质性，年轻患者是否可确诊为马凡综合征还需长期追踪观察。

Identification of a novel mutation of the FBN1 gene in a Chinese family with inherited ectopia lentis

Objective To identify a potential disease-causing mutation in the FBN1 gene in a Chinese family with ectopia lentis （EL）. Methods Case series study. Complete physical， ophthalmic and cardiovascular examinations of all family members were conducted. Peripheral blood samples were collected from the proband and his family members with informed consents. Genomic DNAs were isolated from peripheral blood leukocytes. All 65 exons and exon-intron boundaries of the FBN1 gene were amplified by polymerase chain reaction （PCR）. After purification， the PCR products were bidirectionally sequenced. Results All 3 ectopia lentis individuals were found to carry a novel missense mutation of c.1999T>C （p.Cys 515Arg） in FBN1 that is predicted to be harmful by the SIFT and Polyphen-2， while normal members of the family did not have this mutation. Furthermore， subject Ⅱ-2 and Ⅲ-1 did not show detectable abnormalities in the cardiovascular system compared to Ⅰ-2， who had ascending aorta dilation. Conclusion The EL family patients with the c.1999T>C （p.Cys 515Arg） mutation in the FBN1 gene showed different cardiovascular presentation. However， whether the younger mutation carriers of the family will evolve towards Marfan′s syndrome with aging needs long-term observation.