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Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis

BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known ge...

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Autores principales: Hussain, Hafiz Muhammad Jafar, Cai, Yikai, Weng, Qinjie, Tong, Jun, Aftab, Ayesha, Jin, Yuanmeng, Liu, Jian, Yu, Shuwen, Fang, Zhengying, Du, Wen, Pan, Xiaoxia, Ren, Hong, Xie, Jingyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655905/
https://www.ncbi.nlm.nih.gov/pubmed/36371311
http://dx.doi.org/10.1186/s40246-022-00430-y
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author Hussain, Hafiz Muhammad Jafar
Cai, Yikai
Weng, Qinjie
Tong, Jun
Aftab, Ayesha
Jin, Yuanmeng
Liu, Jian
Yu, Shuwen
Fang, Zhengying
Du, Wen
Pan, Xiaoxia
Ren, Hong
Xie, Jingyuan
author_facet Hussain, Hafiz Muhammad Jafar
Cai, Yikai
Weng, Qinjie
Tong, Jun
Aftab, Ayesha
Jin, Yuanmeng
Liu, Jian
Yu, Shuwen
Fang, Zhengying
Du, Wen
Pan, Xiaoxia
Ren, Hong
Xie, Jingyuan
author_sort Hussain, Hafiz Muhammad Jafar
collection PubMed
description BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known gene mutations. The aim of this study was to investigate the new genetic cause of adult-onset FSGS. METHODS: This study included 40 FSGS families, 77 sporadic FSGS cases, 157 non-FSGS chronic kidney disease (CKD) families and 195 healthy controls for analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed on probands and family members of all recruited families and sporadic FSGS cases. RESULTS: Using WES, we have identified a novel heterozygous missense variant (c.T1655C:p.V552A) in exportin 5 gene (XPO5) in two families (FS-133 and CKD-05) affected with FSGS and CKD. Sanger sequencing has confirmed the co-segregation of this identified variant in an autosomal dominant pattern within two families, while this variant was absent in healthy controls. Furthermore, the identified mutation was absent in 195 ethnically matched healthy controls by Sanger sequencing. Subsequently, in silico analysis demonstrated that the identified variant was highly conservative in evolution and likely to be pathogenic. CONCLUSIONS: Our study reports an adult-onset autosomal dominant inheritance of the XPO5 variant in familial FSGS for the first time. Our study expanded the understanding of the genotypic, phenotypic and ethnical spectrum of mutation in this gene. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40246-022-00430-y.
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spelling pubmed-96559052022-11-15 Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis Hussain, Hafiz Muhammad Jafar Cai, Yikai Weng, Qinjie Tong, Jun Aftab, Ayesha Jin, Yuanmeng Liu, Jian Yu, Shuwen Fang, Zhengying Du, Wen Pan, Xiaoxia Ren, Hong Xie, Jingyuan Hum Genomics Research BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known gene mutations. The aim of this study was to investigate the new genetic cause of adult-onset FSGS. METHODS: This study included 40 FSGS families, 77 sporadic FSGS cases, 157 non-FSGS chronic kidney disease (CKD) families and 195 healthy controls for analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed on probands and family members of all recruited families and sporadic FSGS cases. RESULTS: Using WES, we have identified a novel heterozygous missense variant (c.T1655C:p.V552A) in exportin 5 gene (XPO5) in two families (FS-133 and CKD-05) affected with FSGS and CKD. Sanger sequencing has confirmed the co-segregation of this identified variant in an autosomal dominant pattern within two families, while this variant was absent in healthy controls. Furthermore, the identified mutation was absent in 195 ethnically matched healthy controls by Sanger sequencing. Subsequently, in silico analysis demonstrated that the identified variant was highly conservative in evolution and likely to be pathogenic. CONCLUSIONS: Our study reports an adult-onset autosomal dominant inheritance of the XPO5 variant in familial FSGS for the first time. Our study expanded the understanding of the genotypic, phenotypic and ethnical spectrum of mutation in this gene. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40246-022-00430-y. BioMed Central 2022-11-12 /pmc/articles/PMC9655905/ /pubmed/36371311 http://dx.doi.org/10.1186/s40246-022-00430-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hussain, Hafiz Muhammad Jafar
Cai, Yikai
Weng, Qinjie
Tong, Jun
Aftab, Ayesha
Jin, Yuanmeng
Liu, Jian
Yu, Shuwen
Fang, Zhengying
Du, Wen
Pan, Xiaoxia
Ren, Hong
Xie, Jingyuan
Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title_full Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title_fullStr Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title_full_unstemmed Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title_short Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
title_sort mutation in xpo5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655905/
https://www.ncbi.nlm.nih.gov/pubmed/36371311
http://dx.doi.org/10.1186/s40246-022-00430-y
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