一个马凡综合征家系的FBN1基因新变异及其生物信息学分析

Identification of a novel FBN1 variant in a pedigree affected with Marfan syndrome

目的探讨一个马凡综合征(Marfan syndrome,MFS)家系的遗传学病因,为患者的遗传咨询提供依据.方法收集MFS家系的临床资料,采集先证者及其家系成员的外周血样并提取基因组DNA,经芯片捕获进行高通量测序,筛查变异位点;用Sanger测序法对变异位点进行验证并进行生物信息学分析.结果高通量测序和Sanger测序结果显示该家系患者FBN1基因第7外显子上存在一个错义变异位点c.649T>C(p.Trp217Arg).查阅相关数据库以及文献未见该变异位点致病的报道,确证该变异为新变异.经生物信息学分析,预测该变异致病的可能性较大,可能导致蛋白质二级结构和氨基酸疏水性的改变.结论发现FBN1基因一个新变异位点c.649T>C,该变异可能导致原纤维蛋白-1结构和功能的改变,从而导致常染色体显性遗传的MFS.

Objective To explore the genetic basis for a pedigree affected with Marfan syndrome(MFS).Methods Clinical data of the patients was collected.With genomic DNA extracted from peripheral blood samples,potential mutation was detected by targeted exome sequencing.Candidate variants were validated by Sanger sequencing and bioinformatic analysis.Results Targeted exome sequencing and Sanger sequencing revealed a missense c.649T>C(p.Trp217Arg)variant in the exon 7 of FBN1 gene,which was unreported previously.Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1.Conclusion A novel missense variant of the FBN1 gene was identified,which probably underlies the autosomal dominant MFS in this pedigree.