一个FBN1基因突变的先天性单纯性晶状体异位家系的分析

Analysis of a novel mutation of FBN1 gene in a Chinese family with congenital isolated ectopia lentis

目的分析一个晶状体异位家系的临床特征及致病基因,并探讨基因突变与其临床表型间的关系。方法2018年8月收集晶状体异位家系的临床资料,绘制家系系谱图。采集家系成员的外周静脉血,提取基因组脱氧核糖核酸,应用靶向基因测序方法初步筛选该家系候选突变基因,采用Sanger测序验证和家系共分离分析,确定该家系的致病基因及其突变位点。结果该家系成员共有两代4人。其中,先证者Ⅱ1及其患病母亲分别于6岁及17岁时确诊为双眼晶状体异位,无骨骼系统及心血管系统等异常;先证者Ⅱ1及其患病母亲携带FBN1基因c.1600T>A(p.C534S)杂合突变,生物信息学分析提示具有高致病性,符合家系共分离特征。结论该家系符合先天性单纯性晶状体异位疾病特征;FBN1基因c.1600T>A(p.C534S)是该家系的致病突变,为常染色体显性遗传;该位点突变导致第534号氨基酸由半胱氨酸变异为丝氨酸,此为人群中的首次报道。

Objective The aim of this study was to analyse the clinical characteristics and pathogenic gene of a family with ectopia lentis, and to discuss the genotype-phenotype correlations. Methods Clinical data was collected from a Chinese family with ectopia lentis in August, 2018 and the pedigree chart was drawn. Pathogenic mutation was initially identified from the genomic DNA of peripheral venous blood by targeted gene sequencing(or gene-panel sequencing). All variants were then verified by Sanger sequencing and checked their co-segregation with the phenotypes in the family. Results The pedigree consisted of 2 generations and 4 family members. The proband(Ⅱ1) and his mother were diagnosed as ectopia lentis at the age of 6-and 17-years-old, respectively, while the abnormality of skeletal system and cardiovascular system was not found. These patients with ectopia lentis carried a mutation c.1600 T>A(p.C534 S) in the FBN1 gene,which was predicted to be highly harmful by bioinformatics analysis and in accord with the characteristics of family segregation. Conclusions The patients were diagnosed ascongenital isolated ectopia lentis in the pedigree.The FBN1 c.1600 T>A(p.C534 S) mutation was the pathogenic mutation of this family, which was autosomal dominant inheritance in the family. To the best of our knowledge, it was the first report of the mutation from cysteine to serine of the FBN1 gene for ectopia lentis in humans.