A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series

Abstract Background Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while litt...

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Autores principales:	Jing Wu, Jun Zhang, Li Liu, Bo Zhang, Tomohiko Yamamura, Kandai Nozu, Masafumi Matsuo, Jinghong Zhao
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Alport syndrome COL4A5 Whole exome sequencing Splicing error Minegene assay Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/e59868b416584230bfe8a3f1f70e8be4
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spelling	oai:doaj.org-article:e59868b416584230bfe8a3f1f70e8be42021-11-14T12:43:46ZA disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series10.1186/s12882-021-02585-71471-2369https://doaj.org/article/e59868b416584230bfe8a3f1f70e8be42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12882-021-02585-7https://doaj.org/toc/1471-2369Abstract Background Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants. Methods A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants. Results Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991–14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis. Conclusion A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.Jing WuJun ZhangLi LiuBo ZhangTomohiko YamamuraKandai NozuMasafumi MatsuoJinghong ZhaoBMCarticleAlport syndromeCOL4A5Whole exome sequencingSplicing errorMinegene assayDiseases of the genitourinary system. UrologyRC870-923ENBMC Nephrology, Vol 22, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alport syndrome COL4A5 Whole exome sequencing Splicing error Minegene assay Diseases of the genitourinary system. Urology RC870-923
spellingShingle	Alport syndrome COL4A5 Whole exome sequencing Splicing error Minegene assay Diseases of the genitourinary system. Urology RC870-923 Jing Wu Jun Zhang Li Liu Bo Zhang Tomohiko Yamamura Kandai Nozu Masafumi Matsuo Jinghong Zhao A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
description	Abstract Background Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants. Methods A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants. Results Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991–14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis. Conclusion A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.
format	article
author	Jing Wu Jun Zhang Li Liu Bo Zhang Tomohiko Yamamura Kandai Nozu Masafumi Matsuo Jinghong Zhao
author_facet	Jing Wu Jun Zhang Li Liu Bo Zhang Tomohiko Yamamura Kandai Nozu Masafumi Matsuo Jinghong Zhao
author_sort	Jing Wu
title	A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
title_short	A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
title_full	A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
title_fullStr	A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
title_full_unstemmed	A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
title_sort	disease-causing variant of col4a5 in a chinese family with alport syndrome: a case series
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e59868b416584230bfe8a3f1f70e8be4
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A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series

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