EDM1-PSACH COMP

Contrac.
Disease ID
EDM1, PSACH
Gene ID
COMP
Clinical Links
GARD
45402180
GeneReviews
NBK1123NBK1487
MalaCard
EPP017PSD012
MedGen
98378325376
Mondo
00083220007561
OMIM
132400177170
Orphanet
75093308
Bioinformatical Links
gnomAD
COMP
STRipy
COMP
TR-Atlas
TR155017
WebSTR hg38
1317658
WebSTR hg19
STR_673389

Disease

Pheno. Spec.
Name
Multiple epiphyseal dysplasia, Pseudoachondroplasia
Inheritance
Autosomal dominant
Description
Pseudoachondroplasia is characterized by severe growth deficiency and deformations such as bow legs and hyperlordosis.; Multiple epiphyseal dysplasia type 1 (MED 1) is a form of multiple epiphyseal dysplasia that is characterized by normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early-onset osteoarthrosis. Specific features to MED 1 include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. MED1 is allelic to pseudoachondroplasia with which it shares clinical and radiological features. The disease follows an autosomal dominant mode of transmission1,2 .
Prevalence
Specific contribution of COMP repeats to EDM1 is unknown (~300 COMP mutation variants for both phenotypes); likely 1:90,000 prevalence for COMP-PSACH that is repeat-specific. Found across ancestries/ethnicities3,4 .
Age of OnsetYears3  13
Age of Onset Details
Typical: 0-2 (COMP-PSACH)/ 1-12 (EDM1); Range: 0 (PSACH) - 13 (EDM1). 3-13 specific to trinucleotide expansions (duplications)5 , several contractions but unknown exact AoO3,4 .

Locus

hg19
chr19:18896844-18896859
hg38
chr19:18786034-18786049
t2t
chr19:18921630-18921645
Details
Both expansions to (GTC)6-7 and contractions to (GTC)4 are associated with disease4 .
Mechanism
LoF/GoF?
Poly-aspartic acid expansions, domain dependent5 ; may involve misfolding but still unestablished3 .
Year
19996
Location in Gene
Exon 13
Gene Strand

Alleles

Ref. Motif
GTC
Pathogenic (ref.)
GTC
Pathogenic (gene)
ACG
BenignPathogenicUnits5  56  7

gnomAD

References

Direct supporting references for info on this page.

1
Ontology Lookup Service (OLS)
mondo:0008322
2
Ontology Lookup Service (OLS)
mondo:0007561
3
Multiple Epiphyseal Dysplasia, Autosomal Dominant
Michael D.,Briggs, Michael J.,Wright, Geert R.,Mortier
GeneReviews® · 1993-01-01
genereviews:NBK1123
4
COMP-Related Pseudoachondroplasia
Michael D.,Briggs, Michael J.,Wright
GeneReviews® · 1993-01-01
genereviews:NBK1487
5
Cartilage oligomeric matrix protein: COMPopathies and beyond.
Karen L,Posey, Francoise,Coustry, Jacqueline T,Hecht
Matrix biology : journal of the International Society for Matrix Biology · 2018-03-09
pmid:29530484
6
Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.
E,Délot, L M,King, M D,Briggs, W R,Wilcox, D H,Cohn
Human molecular genetics · 1999-01-01
pmid:9887340

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Medicarpin prevents arthritis in post-menopausal conditions by arresting the expansion of TH17 cells and pro-inflammatory cytokines.
Mohd Nizam,Mansoori, Ashutosh,Raghuvanshi, Priyanka,Shukla, Pallavi,Awasthi, Ritu,Trivedi, Atul,Goel, Divya,Singh
International immunopharmacology · 2020-02-22
pmid:32097846
A B-Z junction induced by an A … A mismatch in GAC repeats in the gene for cartilage oligomeric matrix protein promotes binding with the hZα
Narendar,Kolimi, Yogeeshwar,Ajjugal, Thenmalarchelvi,Rathinavelan
The Journal of biological chemistry · 2017-09-18
pmid:28924040
Identification of novel and recurrent mutations in the calcium binding type III repeats of cartilage oligomeric matrix protein in patients with pseudoachondroplasia.
L H,Cao, L B,Wang, S S,Wang, H W,Ma, C Y,Ji, Y,Luo
Genetics and molecular research : GMR · 2011-05-24
pmid:21644213
Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool.
N,Spassky, Y-G,Han, A,Aguilar, L,Strehl, L,Besse, C,Laclef, M Romaguera,Ros, J M,Garcia-Verdugo, A,Alvarez-Buylla
Developmental biology · 2008-03-04
pmid:18353302
Structure of a thrombospondin C-terminal fragment reveals a novel calcium core in the type 3 repeats.
Marc,Kvansakul, Josephine C,Adams, Erhard,Hohenester
The EMBO journal · 2004-03-11
pmid:15014436
Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects.
Hiroyuki,Kawaji, Gen,Nishimura, Sobei,Watanabe, Akihiko,Mabuchi, Toshiyuki,Ikeda, Hirofumi,Ohashi, Akira,Sasaki, Tokuhisa,Sano, Shiro,Ikegawa
Skeletal radiology · 2002-08-24
pmid:12483437