DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

Osorio Abath; Cristiane de Araújo Martins; Mary Carvalho; Gerson Chadi; Katia Werneck Seitz; Acary Souza Bulle Oliveira; Umbertina Conti Reed; Jocelyn Laporte; Edmar Zanoteli

doi:10.1590/S1415-4757382220140238

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DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

Journal article

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DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

Osorio Abath, Cristiane de Araújo Martins, Mary Carvalho, Gerson Chadi, Katia Werneck Seitz, Acary Souza Bulle Oliveira, Umbertina Conti Reed, Jocelyn Laporte and Edmar Zanoteli

Genetics and molecular biology, Vol.38(2), pp.147-151

05/01/2015

DOI: 10.1590/S1415-4757382220140238

PMCID: PMC4530644

PMID: 26273216

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Abstract

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.

centronuclear myopathy

congenital myopathy

DNM2

dynamin 2

Human and Medical Genetics

Details

Title: Subtitle: DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy
Creators: Osorio Abath - Université de Strasbourg
Cristiane de Araújo Martins - Université de Strasbourg
Mary Carvalho - Universidade de São Paulo
Gerson Chadi - Universidade de São Paulo
Katia Werneck Seitz - Associação de Pais e Amigos dos Excepcionais de São Paulo
Acary Souza Bulle Oliveira - Universidade Federal de São Paulo
Umbertina Conti Reed - Universidade de São Paulo
Jocelyn Laporte - Université de Strasbourg
Edmar Zanoteli - Universidade de São Paulo
Resource Type: Journal article
Publication Details: Genetics and molecular biology, Vol.38(2), pp.147-151
DOI: 10.1590/S1415-4757382220140238
PMID: 26273216
PMCID: PMC4530644
NLM abbreviation: Genet Mol Biol
ISSN: 1415-4757
eISSN: 1678-4685
Publisher: Sociedade Brasileira de Genética
Grant note: 1286/51-2 / CAPES Foundation, Ministry of Education of Brazil
Language: English
Date published: 05/01/2015
Academic Unit: Pathology
Record Identifier: 9984277266702771

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