title: Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region.
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.
  
  
  METHODS
  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.
authors: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors: Na-Yeon
authors: NY
authors: Jung
authors: Department of Neurology, Pusan National University Hospital, Busan, Korea.
authors: Yeong-Eun
authors: YE
authors: Park
authors: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors: Jin-Hong
authors: JH
authors: Shin
authors: Department of Pathology, Pusan National University Hospital, Busan, Korea.
authors: Chang Hun
authors: CH
authors: Lee
authors: Department of Neurology, Pusan National University Hospital, Busan, Korea.
authors: Dae-Soo
authors: DS
authors: Jung
authors: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors: Dae-Seong
authors: DS
authors: Kim
keywords: RYR1; central core disease; core myopathy; ryanodine receptor 1
references: Trends Cardiovasc Med. 2002 Jul;12(5):189-97
references: 12161072
references: Orphanet J Rare Dis. 2007 May 15;2:25
references: 17504518
references: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4164-9
references: 10097181
references: Neuromuscul Disord. 2002 Dec;12(10):930-8
references: 12467748
references: Arch Dis Child. 2003 Dec;88(12):1051-5
references: 14670767
references: J Child Neurol. 2013 Mar;28(3):384-8
references: 22550088
references: Brain. 2007 Aug;130(Pt 8):2024-36
references: 17483490
references: Muscle Nerve. 2007 May;35(5):670-4
references: 17226826
references: Brain. 2006 Jun;129(Pt 6):1470-80
references: 16621918
references: Hum Mol Genet. 2001 Dec 1;10(25):2879-87
references: 11741831
references: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3345-7
references: 10097041
references: J Clin Neurosci. 2012 Jan;19(1):65-70
references: 22030266
references: Hum Mol Genet. 2000 Nov 1;9(18):2599-608
references: 11063719
references: J Biol Chem. 1999 Jan 8;274(2):693-702
references: 9873004
references: Neuromuscul Disord. 2003 Feb;13(2):151-7
references: 12565913
references: J Gen Physiol. 2011 Jan;137(1):43-57
references: 21149547
references: Nature. 1990 Feb 8;343(6258):559-61
references: 1967823
references: Brain. 2003 Nov;126(Pt 11):2341-9
references: 12937085