Key result
DNAJB6 mutations in muscular dystrophy are linked to a reduced capacity to prevent protein aggregation.
Why the study?
The genetic background of unknown muscular dystrophy in five French families was undetermined, motivating investigation of DNAJB6 mutations.
What are the genetic causes of unknown muscular dystrophy in these French families?
Observational (n=12)
What are the genetic causes of unknown muscular dystrophy in these French families?
The study expands the mutational and phenotypic spectrum of DNAJB6-related muscle disease, highlighting its role in distal-onset myopathy and dysphagia.
May warrant DNAJB6 testing in unexplained myopathies; extends spectrum but remains hypothesis-generating.
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.
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Jonson et al. (2018) conducted an observational in Limb girdle muscular dystrophy or distal myopathy (n=12). DNAJB6 mutations was evaluated on Identification of gene mutations and in vitro protein aggregation capacity. Novel and known DNAJB6 mutations were identified in 12 French patients with limb girdle muscular dystrophy or distal myopathy, all showing a reduced capacity to prevent protein aggregation.
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