局灶节段性肾小球硬化一家系COL4A5基因突变研究  

Study of a family affected with focal segmental glomerulosclerosis due to mutation of COL4A5 gene

作　　者：张静[1] 杨静[1] 胡章学[1] 

机构地区：[1]四川大学华西医院肾脏内科,成都610041

出　　处：《中华医学遗传学杂志》2017年第3期373-376,共4页Chinese Journal of Medical Genetics

摘　　要：目的分析1个局灶节段性肾小球硬化（focal segmental glomerulosclerosis, FSGS）家系的遗传学特征，探讨Ⅳ型胶原基因突变与FSGS表型的相关性。方法应用高通量测序方法对1例经临床与肾脏病理诊断为FSGS先证者的相关致病基因进行高通量测序，对发现的疑似致病性突变在先证者及其家系进行Sanger测序验证，并按ACMG指南分析突变的致病性。结果家系先证者的COL4A5基因第28外显子存在1个C．2215C〉G（P．Pr0739Ala）半合子错义突变，先证者母亲为c．2215C〉G杂合突变携带者。c．2215C〉G突变为FSGS的可能致病突变。结论COL4A5基因c．2215C〉G（P．Pr0739Ala）错义突变可导致Alport综合征，也可能导致FSGS，提示Ⅳ型胶原基因突变存在肾脏疾病表型异质性。Objective To analyze the clinicopathoiogic features and genetic mutation in a patient diagnosed with focal segmental glomerulosclerosis （FSGS）. Methods Clinicopathologic data of the patient, who was diagnosed with primary FSGS by renal biopsy, was collected. Mutations of FSGS-related genes were screened with next-generation sequencing. Suspected pathogenic mutation was verified with Sanger sequencing. Results Next-generation sequencing detected a missense mutation （c. 2215C〉G, p. P739A） in exon 28 of the COL4A5 gene in the patient. The same mutation was also detected in his mother who was asymptomatic. Another missense mutation （c. 2215C〉T, p. P739S） in the same codon has been related with Alport syndrome. Conclusion The c. 2215C〉G （p. P739A） mutation may be one of pathogenic mutations underlying FSGS. This has provided further evidence for the phenotypic heterogeneity of COL4A5 gene mutations.

关 键 词：局灶节段性肾小球硬化 COL4A5基因 基因突变 表型异质性 

分 类 号：R440[医药卫生—诊断学] R692[医药卫生—临床医学]