C.P.1 Central core disease with a novel RYR1 mutation in a Korean family

Abstract

Central core disease (CCD) is a form of myopathy inherited autosomal dominantly. It is caused by mutations in RYR1 and allelic to malignant hyperthermia. The diagnosis is established by characteristic muscle pathology and the identification of mutation. Here we report clinical and pathological features of a Korean family with CCD carrying a novel RYR1 mutation. A 15-year-old boy presented with slowly progressive weakness of bilateral legs since school age. The boy could not run and had difficulty in climbing stairs. His muscle weakness slowly progressed and he now has difficulty in rising up from a chair. His mother and sister had markedly milder proximal leg weakness. Diffuse muscle atrophy was noted especially in lower extremities. Muscle power examination disclosed predominantly proximal leg weakness. Serum creatine kinase was within normal limits, and needle electromyography showed active myopathic pattern. Muscle biopsy revealed multiple peripheral and central cores in muscle fibers devoid of oxidative enzyme activities. All the muscle fibers were of type 1. Sequence analysis of RYR1 disclosed a novel mutation in exon 101 (c.14590T>C[p.Tyr4864His]). None of the affected members showed facial muscle weakness or skeletal deformities, although it is said to be frequently accompanied in CCD. Marked difference in clinical severity is noted between proband and his mother; this kind of intrafamilial phenotypic variability had previously been reported in CCD. It has been known that mutations at C-terminal of RYR1 are associated with severe clinical phenotype and clearly demarcated central cores, while mutations outside the C-terminal show milder clinical phenotype and atypical cores in their muscle fiber. Interestingly, the mutation identified in this family is at C-terminal region, all the affected members showed mild phenotype of later-onset and atypical cores inexplicitly ovoid with indistinct borders in the subsarcolemmal areas.