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 of 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

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.

HPO Terms

HP:0000763 Sensory neuropathy HP:0000926 Platyspondyly HP:0001156 Brachydactyly HP:0001249 Intellectual disability HP:0001288 Gait disturbance HP:0001376 Limitation of joint mobility HP:0001377 Limited elbow extension HP:0001382 Joint hypermobility HP:0001385 Hip dysplasia HP:0001387 Joint stiffness HP:0001498 Carpal bone hypoplasia HP:0001763 Pes planus HP:0002341 Cervical cord compression HP:0002515 Waddling gait HP:0002650 Scoliosis HP:0002656 Epiphyseal dysplasia HP:0002663 Delayed epiphyseal ossification HP:0002758 Osteoarthritis HP:0002761 Generalized joint hypermobility HP:0002808 Kyphosis HP:0002812 Coxa vara HP:0002816 Genu recurvatum HP:0002829 Arthralgia HP:0002834 Flared femoral metaphysis HP:0002857 Genu valgum HP:0002938 Lumbar hyperlordosis HP:0002970 Genu varum HP:0003015 Flared metaphysis HP:0003016 Metaphyseal widening HP:0003025 Metaphyseal irregularity HP:0003026 Short long bone HP:0003049 Ulnar deviation of the wrist HP:0003090 Hypoplasia of the capital femoral epiphysis HP:0003093 Limited hip extension HP:0003170 Abnormal acetabulum morphology HP:0003180 Flat acetabular roof HP:0003300 Ovoid vertebral bodies HP:0003301 Irregular vertebral endplates HP:0003311 Hypoplasia of the odontoid process HP:0003312 Abnormal vertebral body morphology HP:0003365 Arthralgia of the hip HP:0003414 Atlantoaxial dislocation HP:0003498 Disproportionate short stature HP:0003502 Mild short stature HP:0003510 Severe short stature HP:0003756 Skeletal myopathy HP:0004019 Radial metaphyseal irregularity HP:0004042 Ulnar metaphyseal irregularity HP:0004236 Irregular carpal bones HP:0004568 Beaking of vertebral bodies HP:0005063 Fragmented, irregular epiphyses HP:0005720 Shortening of all metacarpals HP:0005743 Avascular necrosis of the capital femoral epiphysis HP:0006094 Finger joint hypermobility HP:0006149 Increased laxity of fingers HP:0006429 Broad femoral neck HP:0006460 Ankle hypermobility HP:0006467 Limited shoulder movement HP:0006499 Abnormal femoral epiphysis morphology HP:0008800 Limited hip movement HP:0008807 Acetabular dysplasia HP:0008833 Irregular acetabular roof HP:0008839 Hypoplastic pelvis HP:0008843 Hip osteoarthritis HP:0008873 Disproportionate short-limb short stature HP:0009107 Abnormal ossification involving the femoral head and neck HP:0009487 Ulnar deviation of the hand HP:0009803 Short phalanx of finger HP:0009826 Limb undergrowth HP:0009882 Short distal phalanx of finger HP:0010049 Short metacarpal HP:0010236 Small epiphyses of the phalanges of the hand HP:0010579 Cone-shaped epiphysis HP:0010582 Irregular epiphyses HP:0010585 Small epiphyses HP:0010646 Cervical spine instability HP:0011405 Childhood onset short-limb short stature HP:0012307 Spatulate ribs HP:0020152 Distal joint hypermobility HP:0030839 Knee pain HP:0030840 Ankle pain HP:0030973 Postexertional symptom exacerbation HP:0045086 Knee joint hypermobility HP:0100168 Fragmented epiphyses HP:0100531 Wind-swept deformity of the knees HP:0100864 Short femoral neck

Association

Mendelian

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.

Detection

Year

1999⁶

Location in Gene

Coding Exon 13

Gene Strand

Alleles

Ref. Motif

GTC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CGT

Pathogen. (gene)

ACG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

gnomAD

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

Locus EDM1-PSACH COMP

Disease

Locus

Alleles

gnomAD

References

Additional Literature