Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families.
Eur J Neurol
; 25(5): 790-794, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29437287
ABSTRACT
BACKGROUND AND PURPOSE:
The aim was to determine the genetic background of unknown muscular dystrophy in five French families.METHODS:
Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested in vitro.RESULTS:
Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in DNAJB6 were identified. All showed a reduced capacity to prevent protein aggregation.CONCLUSIONS:
The mutational and phenotypical spectrum of DNAJB6-caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some DNAJB6 mutations cause distal-onset myopathy and hence DNAJB6 defects should be considered broadly in dominant muscular dystrophy families.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Chaperonas Moleculares
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Miopatias Distais
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Distrofia Muscular do Cíngulo dos Membros
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Proteínas de Choque Térmico HSP40
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Mutação
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Eur J Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Finlândia