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...
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2015-06-01
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doaj-ed0a4e569c744b16a09fc5f73ad9054d2020-11-25T01:49:51ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852015-06-0138214715110.1590/S1415-4757382220140238S1415-47572015000200147DNM2 mutations in a cohort of sporadic patients with centronuclear myopathyOsorio Abath NetoCristiane de Araújo MartinsMary CarvalhoGerson ChadiKatia Werneck SeitzAcary Souza Bulle OliveiraUmbertina Conti ReedJocelyn LaporteEdmar ZanoteliCentronuclear 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147&lng=en&tlng=encentronuclear myopathyDNM2dynamin 2congenital myopathy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Osorio Abath Neto Cristiane de Araújo Martins Mary Carvalho Gerson Chadi Katia Werneck Seitz Acary Souza Bulle Oliveira Umbertina Conti Reed Jocelyn Laporte Edmar Zanoteli |
spellingShingle |
Osorio Abath Neto Cristiane de Araújo Martins Mary Carvalho Gerson Chadi Katia Werneck Seitz Acary Souza Bulle Oliveira Umbertina Conti Reed Jocelyn Laporte Edmar Zanoteli DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy Genetics and Molecular Biology centronuclear myopathy DNM2 dynamin 2 congenital myopathy |
author_facet |
Osorio Abath Neto Cristiane de Araújo Martins Mary Carvalho Gerson Chadi Katia Werneck Seitz Acary Souza Bulle Oliveira Umbertina Conti Reed Jocelyn Laporte Edmar Zanoteli |
author_sort |
Osorio Abath Neto |
title |
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_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_sort |
dnm2 mutations in a cohort of sporadic patients with centronuclear myopathy |
publisher |
Sociedade Brasileira de Genética |
series |
Genetics and Molecular Biology |
issn |
1678-4685 |
publishDate |
2015-06-01 |
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. |
topic |
centronuclear myopathy DNM2 dynamin 2 congenital myopathy |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147&lng=en&tlng=en |
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