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DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy
Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sociedade Brasileira de Genética
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530644/ https://www.ncbi.nlm.nih.gov/pubmed/26273216 http://dx.doi.org/10.1590/S1415-4757382220140238 |
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author | Abath, Osorio Martins, Cristiane de Araújo Carvalho, Mary Chadi, Gerson Seitz, Katia Werneck Oliveira, Acary Souza Bulle Reed, Umbertina Conti Laporte, Jocelyn Zanoteli, Edmar |
author_facet | Abath, Osorio Martins, Cristiane de Araújo Carvalho, Mary Chadi, Gerson Seitz, Katia Werneck Oliveira, Acary Souza Bulle Reed, Umbertina Conti Laporte, Jocelyn Zanoteli, Edmar |
author_sort | Abath, Osorio |
collection | PubMed |
description | Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. |
format | Online Article Text |
id | pubmed-4530644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Sociedade Brasileira de Genética |
record_format | MEDLINE/PubMed |
spelling | pubmed-45306442015-08-13 DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy Abath, Osorio Martins, Cristiane de Araújo Carvalho, Mary Chadi, Gerson Seitz, Katia Werneck Oliveira, Acary Souza Bulle Reed, Umbertina Conti Laporte, Jocelyn Zanoteli, Edmar Genet Mol Biol Human and Medical Genetics Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. Sociedade Brasileira de Genética 2015-05 2015-05-01 /pmc/articles/PMC4530644/ /pubmed/26273216 http://dx.doi.org/10.1590/S1415-4757382220140238 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Human and Medical Genetics Abath, Osorio Martins, Cristiane de Araújo Carvalho, Mary Chadi, Gerson Seitz, Katia Werneck Oliveira, Acary Souza Bulle Reed, Umbertina Conti Laporte, Jocelyn Zanoteli, Edmar DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_full |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_fullStr |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_full_unstemmed |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_short |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_sort | dnm2 mutations in a cohort of sporadic patients with centronuclear myopathy |
topic | Human and Medical Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530644/ https://www.ncbi.nlm.nih.gov/pubmed/26273216 http://dx.doi.org/10.1590/S1415-4757382220140238 |
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