Journal
EUROPEAN JOURNAL OF NEUROLOGY
Volume 25, Issue 5, Pages 790-794Publisher
WILEY
DOI: 10.1111/ene.13598
Keywords
genetic and inherited disorders; myopathies; neuromuscular diseases
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Funding
- France Genomique National infrastructure - 'Investissements d'Avenir' programme [ANR-10-INBS-09]
- Fondation Maladies Rares within the Myocapture sequencing project
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Background and purposeThe aim was to determine the genetic background of unknown muscular dystrophy in five French families. MethodsTwelve 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 invitro. ResultsFive patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5years. 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. ConclusionsThe 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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