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c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis
BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are cruc...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342084/ https://www.ncbi.nlm.nih.gov/pubmed/32714376 http://dx.doi.org/10.3389/fgene.2020.00682 |
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author | Jiang, Jingwen Chen, Guang Wu, Jingying Luan, Xinghua Zhou, Haiyan Liu, Xiaoli Zhu, Zeyu Song, Xiaoxuan Wang, Shige Qian, Xiaohang Du, Juanjuan Huang, Xiaojun Zhang, Mei Xu, Wei Cao, Li |
author_facet | Jiang, Jingwen Chen, Guang Wu, Jingying Luan, Xinghua Zhou, Haiyan Liu, Xiaoli Zhu, Zeyu Song, Xiaoxuan Wang, Shige Qian, Xiaohang Du, Juanjuan Huang, Xiaojun Zhang, Mei Xu, Wei Cao, Li |
author_sort | Jiang, Jingwen |
collection | PubMed |
description | BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are crucial for early diagnosis and treatment. OBJECTIVES AND METHODS: Four CTX families with mutations in the CYP27A1 gene were enrolled in our study. We investigated the clinical characteristics and molecular genetic features of the probands with CTX. Genetic analysis was performed for detecting gene variants. Sanger sequencing and segregation analysis were conducted for haplotype analysis. RESULTS: All the four probands were compound heterozygote for two CYP27A1 variants, including one mutation in c.1263+1G>A (intron 7) splice site, two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) and three pathogenic mutations including c.379C>T, c.1263+1G>A and c.1537C>T previously reported. All of the subjects presented with spastic paraparesis. The other common clinical features included ataxia, childhood-onset diarrhea, cataracts, intellectual disability, tendinous xanthomas and dentate nuclei signal alterations at MRI. CONCLUSION: Two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) were reported in our study. The 1263+1G>A mutation was commonly seen in Chinese reported case series (7/25, 28%) and could be a latent hotspot for Chinese CTX mutations. Our study expanded the mutation spectrum of CYP27A1 gene and provide an insightful view of the phenotypic spectrum and genetic characteristics to help early diagnosis and treatment with to improve neurologic dysfunction. |
format | Online Article Text |
id | pubmed-7342084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73420842020-07-24 c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis Jiang, Jingwen Chen, Guang Wu, Jingying Luan, Xinghua Zhou, Haiyan Liu, Xiaoli Zhu, Zeyu Song, Xiaoxuan Wang, Shige Qian, Xiaohang Du, Juanjuan Huang, Xiaojun Zhang, Mei Xu, Wei Cao, Li Front Genet Genetics BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are crucial for early diagnosis and treatment. OBJECTIVES AND METHODS: Four CTX families with mutations in the CYP27A1 gene were enrolled in our study. We investigated the clinical characteristics and molecular genetic features of the probands with CTX. Genetic analysis was performed for detecting gene variants. Sanger sequencing and segregation analysis were conducted for haplotype analysis. RESULTS: All the four probands were compound heterozygote for two CYP27A1 variants, including one mutation in c.1263+1G>A (intron 7) splice site, two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) and three pathogenic mutations including c.379C>T, c.1263+1G>A and c.1537C>T previously reported. All of the subjects presented with spastic paraparesis. The other common clinical features included ataxia, childhood-onset diarrhea, cataracts, intellectual disability, tendinous xanthomas and dentate nuclei signal alterations at MRI. CONCLUSION: Two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) were reported in our study. The 1263+1G>A mutation was commonly seen in Chinese reported case series (7/25, 28%) and could be a latent hotspot for Chinese CTX mutations. Our study expanded the mutation spectrum of CYP27A1 gene and provide an insightful view of the phenotypic spectrum and genetic characteristics to help early diagnosis and treatment with to improve neurologic dysfunction. Frontiers Media S.A. 2020-07-01 /pmc/articles/PMC7342084/ /pubmed/32714376 http://dx.doi.org/10.3389/fgene.2020.00682 Text en Copyright © 2020 Jiang, Chen, Wu, Luan, Zhou, Liu, Zhu, Song, Wang, Qian, Du, Huang, Zhang, Xu and Cao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Jiang, Jingwen Chen, Guang Wu, Jingying Luan, Xinghua Zhou, Haiyan Liu, Xiaoli Zhu, Zeyu Song, Xiaoxuan Wang, Shige Qian, Xiaohang Du, Juanjuan Huang, Xiaojun Zhang, Mei Xu, Wei Cao, Li c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title | c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title_full | c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title_fullStr | c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title_full_unstemmed | c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title_short | c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis |
title_sort | c.1263+1g>a is a latent hotspot for cyp27a1 mutations in chinese patients with cerebrotendinous xanthomatosis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342084/ https://www.ncbi.nlm.nih.gov/pubmed/32714376 http://dx.doi.org/10.3389/fgene.2020.00682 |
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