DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

Genetics and Molecular Biology

Osorio Abath Neto¹  Cristiane De Araújo Martins¹  Mary Carvalho¹  Gerson Chadi¹  Katia Werneck Seitz¹  Acary Souza Bulle Oliveira¹  Umbertina Conti Reed¹  Jocelyn Laporte¹  Edmar Zanoteli¹ 

关键词: centronuclear myopathy;    DNM2;    dynamin 2;    congenital myopathy;   

DOI  :  10.1590/S1415-4757382220140238

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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