一个Usher综合征Ⅰ型家系的临床表型分析及基因诊断

目的筛查一个Usher综合征Ⅰ型家系的致病变异位点,分析其基因型-表型对应关系。方法详细采集先证者的临床表型及家族史,应用高通量测序技术对先证者进行全外显子组检测。应用Sanger测序对疑似致病变异以及家系其他成员的携带情况进行验证。结果先证者10岁时出现夜盲、白内障等症状,之后发生视网膜变性,并随年龄增加出现耳聋症状。高通量测序及Sanger测序提示其携带MYO7A基因c.2694+2T>G及c.6028G>A复合杂合变异。其姐携带相同的变异位点,且表型与先证者相似。先证者女儿携带MYO7A基因c.6028G>A杂合变异,表型无异常。结论明确了一个Usher综合征Ⅰ型家系的遗传学病因,并丰富了该病的表型与基因型数据库,为遗传咨询提供了依据。

Clinical phenotype and genotype analysis of the family with the Usher syndrome

Objective To detect potential variants in a family affected with Usher syndrome type I,and analyze its genotype-phenotype correlation.Methods Clinical data of the family was collected.Potential variants in the proband were detected by high-throughput sequencing.Suspected variants were verified by Sanger sequencing.Results The proband developed night blindness at 10 year old,in addition with bilateral cataract and retinal degeneration.Hearing loss occurred along with increase of age.High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene,namely c.2694+2T>G and c.6028G>A.Her sister carried the same variants with similar clinical phenotypes.Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal.Conclusion The clinical features and genetic variants were delineated in this family with Usher syndrome type I.The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.