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Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy

BACKGROUND: Dysferlinopathy is caused by mutations in the dysferlin (DYSF) gene. Here, we described the genetic features of a large cohort of Chinese patients with this disease. METHODS: Eighty-nine index patients were included in the study. DYSF gene analysis was performed by Sanger sequencing in 4...

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Autores principales: Jin, Su-Qin, Yu, Meng, Zhang, Wei, Lyu, He, Yuan, Yun, Wang, Zhao-Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040013/
https://www.ncbi.nlm.nih.gov/pubmed/27647186
http://dx.doi.org/10.4103/0366-6999.190671
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author Jin, Su-Qin
Yu, Meng
Zhang, Wei
Lyu, He
Yuan, Yun
Wang, Zhao-Xia
author_facet Jin, Su-Qin
Yu, Meng
Zhang, Wei
Lyu, He
Yuan, Yun
Wang, Zhao-Xia
author_sort Jin, Su-Qin
collection PubMed
description BACKGROUND: Dysferlinopathy is caused by mutations in the dysferlin (DYSF) gene. Here, we described the genetic features of a large cohort of Chinese patients with this disease. METHODS: Eighty-nine index patients were included in the study. DYSF gene analysis was performed by Sanger sequencing in 41 patients and targeted next generation sequencing (NGS) in 48 patients. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect exon duplication/deletion in patients with only one pathogenic mutation. RESULTS: Among the 89 index patients, 79 patients were demonstrated to carry two disease-causing (73 cases) or possibly disease-causing mutations (6 cases), including 26 patients with homozygous mutations. We identified 105 different mutations, including 59 novel ones. Notably, in 13 patients in whom only one pathogenic mutation was initially found by Sanger sequencing or NGS, 3 were further identified to carry exon deletions by MLPA. The mutations identified in this study appeared to cluster in the N-terminal region. Mutation types included missense mutations (30.06%), nonsense mutations (17.18%), frameshift mutations (30.67%), in-frame deletions (2.45%), intronic mutations (17.79%), and exonic rearrangement (1.84%). No genotype-phenotype correlation was identified. CONCLUSIONS: DYSF mutations in Chinese patients clustered in the N-terminal region of the gene. Exonic rearrangements were found in 23% of patients with only one pathogenic mutation identified by Sanger sequencing or NGS. The novel mutations found in this study greatly expanded the mutational spectrum of dysferlinopathy.
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spelling pubmed-50400132016-10-12 Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy Jin, Su-Qin Yu, Meng Zhang, Wei Lyu, He Yuan, Yun Wang, Zhao-Xia Chin Med J (Engl) Original Article BACKGROUND: Dysferlinopathy is caused by mutations in the dysferlin (DYSF) gene. Here, we described the genetic features of a large cohort of Chinese patients with this disease. METHODS: Eighty-nine index patients were included in the study. DYSF gene analysis was performed by Sanger sequencing in 41 patients and targeted next generation sequencing (NGS) in 48 patients. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect exon duplication/deletion in patients with only one pathogenic mutation. RESULTS: Among the 89 index patients, 79 patients were demonstrated to carry two disease-causing (73 cases) or possibly disease-causing mutations (6 cases), including 26 patients with homozygous mutations. We identified 105 different mutations, including 59 novel ones. Notably, in 13 patients in whom only one pathogenic mutation was initially found by Sanger sequencing or NGS, 3 were further identified to carry exon deletions by MLPA. The mutations identified in this study appeared to cluster in the N-terminal region. Mutation types included missense mutations (30.06%), nonsense mutations (17.18%), frameshift mutations (30.67%), in-frame deletions (2.45%), intronic mutations (17.79%), and exonic rearrangement (1.84%). No genotype-phenotype correlation was identified. CONCLUSIONS: DYSF mutations in Chinese patients clustered in the N-terminal region of the gene. Exonic rearrangements were found in 23% of patients with only one pathogenic mutation identified by Sanger sequencing or NGS. The novel mutations found in this study greatly expanded the mutational spectrum of dysferlinopathy. Medknow Publications & Media Pvt Ltd 2016-10-05 /pmc/articles/PMC5040013/ /pubmed/27647186 http://dx.doi.org/10.4103/0366-6999.190671 Text en Copyright: © 2016 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Jin, Su-Qin
Yu, Meng
Zhang, Wei
Lyu, He
Yuan, Yun
Wang, Zhao-Xia
Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title_full Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title_fullStr Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title_full_unstemmed Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title_short Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy
title_sort dysferlin gene mutation spectrum in a large cohort of chinese patients with dysferlinopathy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040013/
https://www.ncbi.nlm.nih.gov/pubmed/27647186
http://dx.doi.org/10.4103/0366-6999.190671
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