Ⅳ型胶原α5链基因突变致奥尔波特综合征两家系遗传学分析

目的: 分析奥尔波特（Alport）综合征的遗传学特征。方法: 对原因不明的反复尿检异常的2名先证者进行基于高通量测序技术的全外显子组测序，通过基因突变的致病性、孟德尔遗传规律和临床表型的综合分析，筛选出致病的基因突变，最后通过Sanger测序在家系成员中验证基因突变。结果: 两个家系中分别鉴定出COL4A5基因上的2个杂合性剪接位点突变：c.2147-2A > T（IVS27）和c.646-2A > G（IVS11）（NM_033380），且这2个杂合突变分别与2个家系的患病成员呈现共分离关联。结论: Alport综合征主要通过女性直系患者遗传，临床上可以通过有效的遗传咨询进行产前诊断。

Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families

Objective: To investigate genetic characteristics of Alport syndrome. Methods: High-throughput sequencing-based whole exome sequencing was performed in two patients with recurrent unexplained abnormal urinalysis. The pathogenicity of the genetic variations, type of Mendelian genetics, and clinical phenotypes were analysed, and the disease-cause mutations were confirmed in the family members using Sanger sequencing. Results: Two heterozygous splice site mutations of COL4A5 gene c.2147-2A > T (IVS27) and c.646-2A > G (IVS11) (NM_033380) were found in patients of the two families, which showed a co-segregation association with the affected members of the families. Conclusion: Alport syndrome is mainly inherited from direct female patients, and prenatal genetic screening based on amniotic fluid testing can effectively prevent birth defects in patients with a family history of this characteristic phenotype.