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

doi:10.3785/j.issn.1008-9292.2019.08.06

浙江大学学报（医学版）

2019, Vol. 48

Issue (4): 384-389 DOI: 10.3785/j.issn.1008-9292.2019.08.06

专题报道

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

叶青¹(

),张莹莹²,王晶晶²,毛建华^2,*(

)

1. 浙江大学医学院附属儿童医院实验检验中心, 浙江杭州 310052
2. 浙江大学医学院附属儿童医院肾内科, 浙江杭州 310052

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

YE Qing¹(

),ZHANG Yingying²,WANG Jingjing²,MAO Jianhua^2,*(

)

1. Clinical Laboratory, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
2. Department of Nephrology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China

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摘要：

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。

关键词： 肾炎, 遗传性/遗传学; 胶原Ⅳ型/遗传学; 染色体, 人, X; 外显子; 突变; 系谱; 基因检测; 表型

Abstract:

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.

Key words: Nephritis, hereditary/genetics Collagen type Ⅳ/genetics Chromosomes, human, X Exons Mutation Pedigree Genetic testing Phenotype

收稿日期: 2019-07-20 出版日期: 2019-10-30

R349.3

基金资助: 国家自然科学基金(81501760, 81470939, 81770710)

通讯作者: 毛建华 E-mail: qingye@zju.edu.cn;maojh88@zju.edu.cn

作者简介: 叶青(1983—), 男, 博士, 副主任技师, 主要从事儿童疾病致病机制研究; E-mail: qingye@zju.edu.cn; https://orcid.org/0000-0002-5614-2695

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引用本文:

叶青,张莹莹,王晶晶,毛建华. 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[J]. 浙江大学学报（医学版）, 2019, 48(4): 384-389.

YE Qing,ZHANG Yingying,WANG Jingjing,MAO Jianhua. Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families. J Zhejiang Univ (Med Sci), 2019, 48(4): 384-389.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.08.06 或 http://www.zjujournals.com/med/CN/Y2019/V48/I4/384

图 1 X染色体连锁Alport综合征家系图

图 2 X染色体连锁Alport综合征家系先证者肾组织HE染色和透射电镜图

表 1 Alport综合征两家系患病成员临床资料和实验室检查结果

图 3 X染色体连锁Alport综合征家系中的先证者COL4A5基因突变位点Sanger测序图

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