G.P.13.10 High frequency of polymorphisms in the RYR1 gene in Brazilian patients with centronuclear myopathy (original) (raw)

2008, Neuromuscular Disorders

weakness. The onset of the disease was in both cases during early childhood, followed by a mild progressive deterioration during adulthood. Physical examination of the patients showed elongated face, typical skeletal abnormalities like congenital hip dislocation, foot deformities, thoraco-lumbar scoliosis, bilateral atrophy of calf and tibialis anterior, scapular winging, Gowers' sign, mild facial weakness, normal strength of the upper limbs, marked weakness of ileo-psoas, moderate weakness of quadriceps, tibialis anterior, extensors and flexors digitorum. Serum CK was normal and an electromyographic study showed myopathic findings. Muscle biopsy showed fibre size variation with hypertrophic and angular hypotrophic fibres and a large number of internally located nuclei. Oxidative enzyme stains showed central and eccentric cores in the majority of fibres mildly positive to esterase reaction. An increase in lysosomial activity especially around the cores was also observed. Analysis of RYR1 gene showed a mutation in exon 85 (c.11708G>A; p.R3903Q): in the two affected daughters the mutation was present in homozygous form, the parents were heterozygotic. Our data suggest the hypothesis that the same mutation present in different state (homozygous versus heterozygous) can give rise to a different phenotype (CCD versus MH) implying that mutations in homozygous state can severely affect the tetrameric RyR1 protein.

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