独立型常染色体显性多囊肝家系的临床及遗传学分析

Clinical and genetic analysis of autosomal dominant polycystic liver disease

目的对一个多囊肝家系进行临床及致病基因变异分析,明确其遗传学病因。方法收集先证者临床资料和家族史,应用全外显子组测序技术对先证者进行基因变异检测;针对筛选出的致病性基因变异对先证者及其家系成员进行荧光定量PCR验证。结果一男性先证者,18岁体检时发现肝脏多发囊肿,肝功能未见异常,其父亲和祖父肝脏均存在多发囊肿,无明显不适,余无特殊。全外显子组测序提示先证者SEC63基因第1外显子(Exon1)存在杂合缺失,实时荧光定量PCR证实先证者SEC63基因Exon1杂合缺失变异来自其父亲,其祖父检测到相同杂合缺失。根据美国医学遗传学与基因组学学会指南,该基因变异为致病变异,之前鲜见报道。结论明确了该常染色体显性多囊肝家系的遗传学病因,SEC63基因Exon1杂合缺失为新发现的基因变异,该变异拓宽了SEC63基因变异谱。

ObjectiveTo analyze and clarify the clinical and pathogenic gene variation and genetic etiology of polycystic liver disease.MethodsThe proband clinical data and family history were collected.Whole-exome sequencing technology was used to detect the proband gene variations.Fluorescence quantitative PCR validation was performed on the proband and his family to screen out pathogenic gene variation.ResultsA multiple liver cyst was found in an 18-year-old male proband during a physical examination.There were no abnormalities in his liver function,and both his father and grandfather had multiple liver cysts without any obvious discomfort or other special manifestations.Whole exome sequencing suggested a heterozygous deletion in exon 1(Exon 1)of the SEC63 gene in the proband.Real-time fluorescence quantitative PCR confirmed that the heterozygous deletion variation of the SEC63 gene Exon 1 of the proband came from his father,and the same heterozygous deletion was detected in his grandfather.The gene variant had a pathogenic variation that had been rarely reported before and was in accordance with the the American college of Medical Genetics and Genomics(ACMG)guidelines.ConclusionsThe genetic etiology of this autosomal dominant polycystic liver disease has been clarified,and the heterozygous deletion of Exon1 of the SEC63 gene is a newly discovered gene variation that broadens the variation spectrum of the SEC63 gene.