A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function.
Clin Genet
; 92(2): 150-157, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28233300
ABSTRACT
BACKGROUND:
Mutations in the DNAJB6 gene have been identified as a rare cause of dominantly inherited limb-girdle muscular dystrophy or distal-onset myopathy. MATERIALS ANDMETHODS:
Exome sequencing was performed to investigate a Taiwanese family with a dominantly inherited distal-onset myopathy. Functional effects of the causal mutation were investigated in vitro.RESULTS:
Exome sequencing of the two affected individuals in this family identified a heterozygous mutation, c.287C>T (p.Pro96Leu) in the DNAJB6 gene, which co-segregated with the myopathy within all 12 family members. Notably, this mutation is novel and localizes within the glycine and phenylalanine-rich (G/F) domain and alters an amino acid residue previously reported with a different mutation. Furthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein.CONCLUSION:
This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Chaperonas Moleculares
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Predisposição Genética para Doença
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Miopatias Distais
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Proteínas de Choque Térmico HSP40
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Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article