Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. - Archive ouverte HAL Access content directly
Journal Articles Neuromuscular Disorders Year : 2007

Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.

Heinz Jungbluth
  • Function : Author
Haiyan Zhou
  • Function : Author
Caroline A Sewry
  • Function : Author
Stephanie Robb
  • Function : Author
Susan Treves
  • Function : Author
Marc Bitoun
Carsten Bönnemann
  • Function : Author
Francesco Muntoni

Abstract

Centronuclear myopathy is a genetically heterogeneous congenital myopathy. Whilst mutations in the myotubularin (MTM1) gene are implicated in the X-linked variant, mutations in the dynamin 2 (DNM2) gene have been recently associated with dominant inheritance. We report a 16-year-old girl with clinical features of a congenital myopathy and external ophthalmoplegia. Multiple central nuclei affecting up to 50% of fibres and central accumulation of oxidative enzyme stains were the most prominent findings on muscle biopsy obtained at 1 year. However, some core-like areas appeared on repeat biopsy 8 years later; in addition, muscle MRI was compatible with the pattern we previously reported in patients with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Mutational analysis identified a de novo dominant RYR1 missense mutation (c.12335C>T; Ser4112Leu) affecting a highly conserved domain of the protein. Our findings expand the phenotypical spectrum associated with RYR1 mutations and indicate that RYR1 screening should be considered in centronuclear myopathy patients without MTM1 or DNM2 mutations; muscle MRI may aid selection of appropriate genetic testing.

Dates and versions

hal-00189980 , version 1 (22-11-2007)

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Heinz Jungbluth, Haiyan Zhou, Caroline A Sewry, Stephanie Robb, Susan Treves, et al.. Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.. Neuromuscular Disorders, 2007, 17 (4), pp.338-45. ⟨10.1016/j.nmd.2007.01.016⟩. ⟨hal-00189980⟩
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