EDM1-PSACH COMP

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 transmission^1,2.

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/ethnicities^3,4.

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 AoO^3,4.

Locus

hg19

chr19:18896844-18896860

hg38

chr19:18786034-18786050

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

gnomAD

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008322

Ontology Lookup Service (OLS)

mondo:0007561

Multiple Epiphyseal Dysplasia, Autosomal Dominant

Michael D.,Briggs, Michael J.,Wright, Geert R.,Mortier

GeneReviews® · 1993-01-01

genereviews:NBK1123

COMP-Related Pseudoachondroplasia

Michael D.,Briggs, Michael J.,Wright

GeneReviews® · 1993-01-01

genereviews:NBK1487

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

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