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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (4): 384-389    DOI: 10.3785/j.issn.1008-9292.2019.08.06
    
Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families
YE Qing1(),ZHANG Yingying2,WANG Jingjing2,MAO Jianhua2,*()
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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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     
Received: 20 July 2019      Published: 30 October 2019
CLC:  R349.3  
  R725  
Corresponding Authors: MAO Jianhua     E-mail: qingye@zju.edu.cn;maojh88@zju.edu.cn
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YE Qing
ZHANG Yingying
WANG Jingjing
MAO Jianhua
Cite this article:

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.

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


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。


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 
Fig 1 Pedigree of the families with X-linked Alport syndrome
Fig 2 Pathological changes in renal tissue of proband of X-linked Alport syndrome
序号 听力 视力 血压(mmHg) 尿红细胞 尿蛋白 尿素(mmol/L) 肌酐(μmol/L) 血白蛋白(g/L) 血球蛋白(g/L) 总胆固醇(mmol/L) 三酰甘油(mmol/L)
1 mmHg=0.133 kPa.
家系1 Ⅰ2 正常 正常 142/90 ++ ++ 5.2 78 39 28 6.2 2.3
Ⅱ5 正常 正常 正常 ++ ++ 3.2 62 34 21 5.7 1.9
Ⅲ6 正常 正常 正常 +++ + 4.1 68 42 31 3.2 1.5
家系2 Ⅰ2 正常 正常 正常 ++ ++ 4.8 54 37 24 5.9 3.2
Ⅱ5 正常 正常 正常 + + 12.5 782 41 30 6.3 1.4
Ⅲ5 正常 正常 正常 +++ ++ 5.7 73 35 22 4.5 1.1
Ⅲ6 正常 正常 正常 +++ + 4.9 41 43 34 4.2 1.6
Tab 1 Clinical data and laboratory examination of two families with Alport syndrome
Fig 3 Sanger sequencing of COL4A5 gene variation locus in proband of X-linked Alport syndrome
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