Details of Disease

General Information of Disease (ID: DIS5FZLR)

• Disease Name: Multiple epiphyseal dysplasia
• Synonyms: epiphyseal dysplasia, multiple; Dominant Multiple Epiphyseal Dysplasia; EDM; Polyepiphyseal dysplasia; MED; multiple epiphyseal dysplasia (disease); polyepiphyseal dysplasia; multiple epiphyseal dysplasia
• Definition: Multiple epiphyseal dysplasias (MED/EDMs) are characterized by epiphyseal anomalies causing joint pain early in life, recurrent osteochondritis and early arthrosis. The EDMs are a heterogeneous group of diseases with variable expression classed as MED/EDMs 1-6.
• Disease Hierarchy:
  DIS9SPWW: Osteochondrodysplasia
  DIS5Z8U6: Skeletal dysplasia
  DIS5FZLR: Multiple epiphyseal dysplasia
• Disease Identifiers:
  MONDO ID: MONDO_0016648
  MESH ID: D010009
  UMLS CUI: C0026760
  MedGen ID: 6461
  HPO ID: HP:0002654
  Orphanet ID: 251
  SNOMED CT ID: 59708000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DLL3	TT1C9K6	Limited	Biomarker	[1]
FLT1	TT1VAUK	Limited	Biomarker	[2]
GLB1	TTNGJPH	Limited	Biomarker	[3]
KDR	TTUTJGQ	Limited	Biomarker	[2]
TRPV4	TTKP2SU	Disputed	Biomarker	[4]
FLNA	TTSTRZY	Strong	Biomarker	[5]
HSPG2	TT5UM29	Strong	Biomarker	[6]
MANF	TT56RYE	Strong	Biomarker	[7]
SCN8A	TT54ERL	Strong	Genetic Variation	[8]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A2	DTFSLX5	Strong	Genetic Variation	[9]
SLC26A5	DTPGHJ7	Strong	Biomarker	[10]
SLC26A2	DTFSLX5	Definitive	Autosomal recessive	[11]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHST3	DEQIZP2	Limited	Biomarker	[12]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COL11A1	OTB0DRMS	Limited	Biomarker	[13]
COL9A1	OTWBR27Y	Limited	Genetic Variation	[14]
COL2A1	OT5E59C8	moderate	Biomarker	[15]
KIF7	OT1J6NAW	moderate	Genetic Variation	[16]
ADAMTSL2	OTAXNV2U	Strong	Biomarker	[17]
CANT1	OT1TPWQR	Strong	Genetic Variation	[18]
COL9A2	OT1ZBDBV	Strong	Biomarker	[19]
CRELD2	OTL73AO8	Strong	Biomarker	[20]
IFT81	OTB23T17	Strong	Genetic Variation	[21]
MATN3	OTH9H74J	Strong	Genetic Variation	[22]
COMP	OTS2FPMI	Definitive	Autosomal dominant	[11]
SLC26A2	OTJNHNTO	Definitive	Autosomal recessive	[11]

References

• [1] Mapping of the autosomal recessive (AR) craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation of genetic heterogeneity for mild AR spondylocostal dysplasia.Am J Med Genet. 2000 Dec 18;95(5):482-91. doi: 10.1002/1096-8628(20001218)95:5<482::aid-ajmg14>3.0.co;2-x.
• [2] Thiram-induced changes in the expression of genes relating to vascularization and tibial dyschondroplasia.Poult Sci. 2007 Nov;86(11):2390-5. doi: 10.3382/ps.2007-00219.
• [3] Spondyloepiphyseal dysplasia, corneal clouding, normal intelligence and acid beta-galactosidase deficiency.Clin Genet. 1976 May;9(5):495-504. doi: 10.1111/j.1399-0004.1976.tb01603.x.
• [4] Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat Genet. 2008 Aug;40(8):999-1003. doi: 10.1038/ng.166. Epub 2008 Jun 29.
• [5] Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003 Apr;33(4):487-91. doi: 10.1038/ng1119. Epub 2003 Mar 3.
• [6] Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet. 2001 Apr;27(4):431-4. doi: 10.1038/86941.
• [7] Mesencephalic astrocyte-derived neurotropic factor is an important factor in chondrocyte ER homeostasis.Cell Stress Chaperones. 2019 Jan;24(1):159-173. doi: 10.1007/s12192-018-0953-7. Epub 2018 Dec 12.
• [8] Model systems for studying skeletal dysplasias caused by TSP-5/COMP mutations.Cell Mol Life Sci. 2008 Mar;65(5):687-99. doi: 10.1007/s00018-007-7485-0.
• [9] Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia.Am J Med Genet A. 2019 Apr;179(4):534-541. doi: 10.1002/ajmg.a.61049. Epub 2019 Feb 10.
• [10] Pathogenetics of the human SLC26 transporters.Curr Med Chem. 2005;12(4):385-96. doi: 10.2174/0929867053363144.
• [11] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [12] Whole exome sequencing detects CHST3 mutation in patient with acute promyelocytic leukemia: A case report.Medicine (Baltimore). 2018 Sep;97(36):e12214. doi: 10.1097/MD.0000000000012214.
• [13] Craniofacial cartilage morphogenesis requires zebrafish col11a1 activity.Matrix Biol. 2009 Oct;28(8):490-502. doi: 10.1016/j.matbio.2009.07.004. Epub 2009 Jul 26.
• [14] Exome-wide copy number variation analysis identifies a COL9A1 in frame deletion that is associated with hearing loss.Eur J Med Genet. 2019 Oct;62(10):103724. doi: 10.1016/j.ejmg.2019.103724. Epub 2019 Jul 14.
• [15] A mutation in the amino-terminal end of the triple helix of type II collagen causing severe osteochondrodysplasia.Genomics. 1993 Apr;16(1):282-5. doi: 10.1006/geno.1993.1179.
• [16] A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. Orphanet J Rare Dis. 2012 May 15;7:27. doi: 10.1186/1750-1172-7-27.
• [17] ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199.
• [18] MED resulting from recessively inherited mutations in the gene encoding calcium-activated nucleotidase CANT1.Am J Med Genet A. 2017 Sep;173(9):2415-2421. doi: 10.1002/ajmg.a.38349. Epub 2017 Jul 25.
• [19] Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.Am J Med Genet A. 2010 Apr;152A(4):863-9. doi: 10.1002/ajmg.a.33240.
• [20] Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for ... Hum Mol Genet. 2013 Dec 20;22(25):5262-75.
• [21] Alu-Alu mediated intragenic duplications in IFT81 and MATN3 are associated with skeletal dysplasias.Hum Mutat. 2018 Oct;39(10):1456-1467. doi: 10.1002/humu.23605. Epub 2018 Aug 22.
• [22] XBP1 signalling is essential for alleviating mutant protein aggregation in ER-stress related skeletal disease.PLoS Genet. 2019 Jul 1;15(7):e1008215. doi: 10.1371/journal.pgen.1008215. eCollection 2019 Jul.