J Clin Neurol.  2015 Jan;11(1):97-101. 10.3988/jcn.2015.11.1.97.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region

• Jung NY
• Park YE
• Shin JH
• Lee CH
• Jung DS
• Kim DS

• KMID: 2179580
• DOI: http://doi.org/10.3988/jcn.2015.11.1.97

Abstract

BACKGROUND
Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients.
CASE REPORT
Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A).
CONCLUSIONS
We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

Keyword

central core disease; ryanodine receptor 1; RYR1; core myopathy

MeSH Terms

Biopsy
Congenital Abnormalities
Exons
Facial Muscles
Humans
Muscle Weakness
Muscular Diseases
Mutation, Missense
Myopathy, Central Core*
Phenotype
Ryanodine Receptor Calcium Release Channel*
Sequence Analysis
Ryanodine Receptor Calcium Release Channel

Figure

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  Fig. 1 A: The pedigrees of case 1 and case 2. Arrows indicate the probands of each family. B: Chromatograms showing sequence changes. The left chromatogram from case 1 (left) shows the aberrant 'C' peak, which is slightly larger than the normal 'T' peak (c.14590T>C). The right chromatogram from case 2 shows a normal 'G' peak, which is larger than the aberrant 'A' peak (c.14678G>A).

• 

  Fig. 2 Muscle sections from case 1. A and B: Multiple peripheral and central cores are characterized by an inexplicit ovoid shape and indistinct borders (A: Nicotinamide dehydrogenase-tetrazolium reductase stain, ×200; B: Cytochrome C oxidase, ×200). C: All of the muscle fibers were of type 1 (C: Adenosine triphosphatase, pH 4.4, ×200). D: Electron micrograph showing a core region lined by arrowheads. The myofibrils are disorganized (arrows) compared with those within intact fibers.

• 

  Fig. 3 Muscle sections from case 2. A and B: These slides exhibit peripheral and central cores (A: Nicotinamide dehydrogenase-tetrazolium reductase, ×200; B: Cytochrome C oxidase, ×200). C: Staining with adenosine triphosphatase (pH 4.4, ×100) reveals selective type-1 fiber atrophy. D: Electron micrograph showing a core region (arrows) characterized by disruption of the myofibrillar organization.

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