两个马凡综合征家系的FBN1基因突变分析

Analysis of FBN1 gene mutations in two pedigrees affected with Marfan syndrome

目的 对两个马凡综合征家系进行原纤维蛋白基因-1(fibrillin-1 gene,FBN1)基因突变的筛查分析.方法 采集家系中患者及正常个体外周静脉血,提取基因组DNA.应用二代测序法对FBN1基因全部65个外显子进行序列分析.应用PolyPhen-2和SIFT预测FBN1蛋白可能的结构和功能变化.结果 两家系的患者均表现出眼部和骨骼系统的症状;测序结果显示两家系患者分别携带FBN1基因c.1879C>T(p.R627C)、c.2584T>C(p.C862R)杂合错义突变,家系中其他正常成员均未检出该突变.PolyPhen-2和SIFT预测该突变位点可能导致FBN1蛋白的结构和功能受到破坏.结论 两个家系中的FBN1基因c.1879C>T及c.2584T>C突变,可能是患者致病的原因;其中c.2584T>C基因突变在中国马凡综合征患者中尚未见报道.本研究结果丰富了FBN1基因的突变谱,为该家系的遗传咨询和产前诊断提供了依据.

Objective To detect mutations of fibrillin 1(FBN1)gene in two pedigrees affected with Marfan syndrome(MFS).Methods Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA.All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing.PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein.Results Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS.Two novel heterozygous mutations of the FBN1 gene,including c.1879C>T(p.R627C)in exon 16 and c.2584T>C(p.C862R)in exon 22,were identified.The same mutations were not found among unaffected members.By bioinformatic analysis,the mutations may affect the structure and function of the FBN1 protein.Conclusion The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees,respectively.The c.2584T>C has enriched the spectrum of FBN1 gene mutations.