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- Title
Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families.
- Authors
Jonson, P. H.; Palmio, J.; Johari, M.; Penttil#228;, S.; Evil#228;, A.; Nelson, I.; Bonne, G.; Wiart, N.; Meyer, V.; Boland, A.; Deleuze, J.-F.; Masson, C.; Stojkovic, T.; Chapon, F.; Romero, N. B.; Sol#233;, G.; Ferrer, X.; Ferreiro, A.; Hackman, P.; Richard, I.
- 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.
- Publication
European Journal of Neurology, 2018, Vol 25, Issue 5, p790
- ISSN
1351-5101
- Publication type
Article
- DOI
10.1111/ene.13598