A novel splicing mutation identified in a Chinese family with Alport syndrome and analysis of its pathogenicity
10.16571/j.cnki.1008-8199.2019.06.012
- VernacularTitle: 一个中国Alport综合征家系中剪接突变及致病性分析
- Author:
Xing LÜ
1
;
Wei-qing WU
1
;
Ying-xia CUI
1
;
Fang-fang CHEN
1
;
Ning SUN
1
;
Xin-yue YAO
1
;
Zheng-kun XIA
1
;
Zhi-hong LIU
1
;
Xiao-jun LI
1
Author Information
1. Medical School of Jiangsu University, Zhenjiang 212013, Jiangsu, China; Institute of Clinical Laboratory Medicine of PLA,General Hospital of Eastern Theater Command,PLA, Nanjing 210002, Jiangsu, China; Department of Pediatrics,General Hospital of Eastern Theater Command,PLA, Nanjing 210002, Jiangsu, China; Department of Nephrology, General Hospital of Eastern Theater Command,PLA, Nanjing 210002, Jiangsu, China
- Publication Type:Journal Article
- Keywords:
Alport syndrome;
splicing mutation;
high throughput sequencing;
minigene
- From:
Journal of Medical Postgraduates
2019;32(6):619-623
- CountryChina
- Language:Chinese
-
Abstract:
Objective The purpose of this study was to identify a pathogenic variant in a Chinese family with Alport syndrome and analyze the pathogenicity of the variant. Methods Using targeted region capture and high-throughput sequencing technology, we identified the genetic variant of the proband with Alport syndrome, verified the variant in the family members by Sanger sequencing, and analyzed its influence on the pre-mRNA splicing process by in vitro minigene assay. Results A heterozygous variant c.2767G>T (p.Gly923Cys) was identified as a novel variant in exon 32 of the COL4A5 gene in the proband, which was confirmed by Sanger sequencing to be cosegregated with disease in the family. The minigene assay demonstrated that the c.2767G>T variant induced deletion of exon 32 of the COL4A5 gene. Conclusion A novel COL4A5 mutation was identified by targeted region capture and high-throughput sequencing, which has enriched the gene mutation spectrum of Alport syndrome. The exonic mutation c.2767G>T confirmed to be a splicing mutation by in vitro minigene assay, which may lead to a deeper insight into the molecular pathogenesis of Alport syndrome.
