Details of Disease

General Information of Disease (ID: DIS18AZZ)

• Disease Name: Central core myopathy
• Synonyms: Cco; Shy-Magee syndrome; myopathy, central core; multiminicore disease, moderate, with hand involvement; central CORE disease of muscle; muscular central core disease; neuromuscular disease, congenital, with uniform type 1 Fibre; muscle core disease; multicore myopathy, moderate, with hand involvement; neuromuscular disease, congenital, with uniform type 1 Fiber; myopathy, central fibrillar; minicore myopathy, moderate, with hand involvement; CCD; central core disease
• Definition: An autosomal dominant congenital disorder affecting the skeletal muscles. Microscopically, it is characterized by disorganized areas, which are called cores, seen usually in the center of the muscle fibers. Clinically it presents as mild to severe muscle weakness. It may be associated with skeletal abnormalities including scoliosis, joint deformities, and hip dislocation.
• Disease Hierarchy:
  DISF24LW: Myofibrillar myopathy
  DIS7PCBA: TPM2-related myopathy
  DISIRF54: RYR1-related myopathy
  DIS18AZZ: Central core myopathy
• Disease Identifiers:
  MONDO ID: MONDO_0007294
  MESH ID: D020512
  UMLS CUI: C0751951
  OMIM ID: 117000
  MedGen ID: 199773
  Orphanet ID: 597
  SNOMED CT ID: 43152001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FKBP1A	TTMW94E	Limited	Biomarker	[1]
CACNA1S	TT94HRF	Strong	Biomarker	[2]
EPHA3	TTHS2LR	Strong	Genetic Variation	[3]
MYH7	TTNIMDP	Strong	Biomarker	[4]
RYR1	TTU5CIX	Strong	Autosomal dominant	[5]
RYR1	TTU5CIX	Definitive	Genetic Variation	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A3	DTN1FMD	Limited	Biomarker	[7]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHKB	DEHWR6V	Strong	Biomarker	[8]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP2A1	OT959A3A	Limited	Altered Expression	[9]
MED25	OTDBY87B	Limited	Altered Expression	[10]
MYL3	OTKD3RSX	Limited	Altered Expression	[11]
MYOT	OTCEW5XW	Limited	Biomarker	[12]
RYR2	OT0PF19E	Limited	Genetic Variation	[13]
B4GAT1	OT5NH9TD	Strong	Biomarker	[14]
FKRP	OTMUZ7GH	Strong	Biomarker	[15]
FKTN	OTQ9GCXL	Strong	Biomarker	[16]
ITGA7	OTTBTAYW	Strong	Biomarker	[17]
LARGE1	OTUH7H9F	Strong	Biomarker	[18]
LMNA	OT3SG7ZR	Strong	Genetic Variation	[19]
POMGNT1	OTBNOUZC	Strong	Biomarker	[15]
RYR1	OTWUB65S	Strong	Autosomal dominant	[5]
SELENON	OTSGKO5M	Strong	Genetic Variation	[20]

References

• [1] Central core disease is due to RYR1 mutations in more than 90% of patients.Brain. 2006 Jun;129(Pt 6):1470-80. doi: 10.1093/brain/awl077. Epub 2006 Apr 18.
• [2] Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum.Biochim Biophys Acta. 2011 May;1813(5):948-64. doi: 10.1016/j.bbamcr.2010.11.009. Epub 2010 Nov 27.
• [3] Ca2+ signaling in HEK-293 and skeletal muscle cells expressing recombinant ryanodine receptors harboring malignant hyperthermia and central core disease mutations.J Biol Chem. 2005 Apr 15;280(15):15380-9. doi: 10.1074/jbc.M410421200. Epub 2005 Feb 2.
• [4] Autosomal dominant eccentric core disease caused by a heterozygous mutation in the MYH7 gene.J Neurol Neurosurg Psychiatry. 2014 Oct;85(10):1149-52. doi: 10.1136/jnnp-2013-306754. Epub 2014 May 14.
• [5] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [6] Homozygous/compound heterozygote RYR1 gene variants: Expanding the clinical spectrum.Am J Med Genet A. 2019 Mar;179(3):386-396. doi: 10.1002/ajmg.a.61025. Epub 2019 Jan 16.
• [7] Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.J Pediatr. 2019 Nov;214:151-157.e6. doi: 10.1016/j.jpeds.2019.07.039. Epub 2019 Aug 30.
• [8] A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis.J Biol Chem. 2006 Feb 24;281(8):4938-48. doi: 10.1074/jbc.M512578200. Epub 2005 Dec 21.
• [9] Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels.J Biol Chem. 1999 Jan 8;274(2):693-702. doi: 10.1074/jbc.274.2.693.
• [10] Structural development of a type-1 ryanodine receptor (RyR1) Ca(2+)-release channel inhibitor guided by endoplasmic reticulum Ca(2+) assay.Eur J Med Chem. 2019 Oct 1;179:837-848. doi: 10.1016/j.ejmech.2019.06.076. Epub 2019 Jun 29.
• [11] Myosin light chain gene expression associated with disease states of the human heart.J Mol Cell Cardiol. 1993 May;25(5):577-85. doi: 10.1006/jmcc.1993.1067.
• [12] Beyond LGMD1A: myotilin is a component of central core lesions and nemaline rods.Neuromuscul Disord. 2003 Aug;13(6):451-5. doi: 10.1016/s0960-8966(03)00064-6.
• [13] Reduced threshold for store overload-induced Ca(2+) release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.Biochem J. 2017 Aug 7;474(16):2749-2761. doi: 10.1042/BCJ20170282.
• [14] Dystroglycan organizes axon guidance cue localization and axonal pathfinding.Neuron. 2012 Dec 6;76(5):931-44. doi: 10.1016/j.neuron.2012.10.009.
• [15] Degree of Cajal-Retzius Cell Mislocalization Correlates with the Severity of Structural Brain Defects in Mouse Models of Dystroglycanopathy.Brain Pathol. 2016 Jul;26(4):465-78. doi: 10.1111/bpa.12306. Epub 2015 Oct 12.
• [16] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.Hum Mol Genet. 2009 Feb 15;18(4):621-31. doi: 10.1093/hmg/ddn387. Epub 2008 Nov 18.
• [17] 61 and 71 integrins are required in Schwann cells to sort axons.J Neurosci. 2013 Nov 13;33(46):17995-8007. doi: 10.1523/JNEUROSCI.3179-13.2013.
• [18] Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases.Mol Cell Neurosci. 2005 Oct;30(2):160-72. doi: 10.1016/j.mcn.2005.07.009.
• [19] A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy.Int Heart J. 2018 May 30;59(3):531-541. doi: 10.1536/ihj.17-377. Epub 2018 May 6.
• [20] Mutations in MYH7 cause Multi-minicore Disease (MmD) with variable cardiac involvement.Neuromuscul Disord. 2012 Dec;22(12):1096-104. doi: 10.1016/j.nmd.2012.06.007. Epub 2012 Jul 10.