Epiphyseal Dysplasia, Multiple, 1 (COMP)
| Dred_ID | RD00013 |
| OMIM ID | 132400 |
| Disease name | Epiphyseal Dysplasia, Multiple, 1 |
| Alternative names | EDM1 Epiphyseal Dysplasia-1 |
| Category | Genetic diseases, Rare diseases, Bone diseases, Fetal diseases |
| Phenotype | NIH Rare Diseases: Pseudoachondroplasia is an inherited disorder of bone growth which is characterized by short stature. Other features include short arms and legs, a waddling walk, early-onset joint pain (osteoarthritis), and a limited range of motion at the elbows and hips. Intelligence, facial features and head size are normal. Pseudoachondroplasia is caused by mutations in the COMP gene. This condition is inherited in an autosomal dominant pattern. OMIM: Pseudoachondroplasia is an autosomal dominant osteochondrodysplasia characterized by disproportionate short stature, deformity of the lower limbs, brachydactyly, loose joints, and ligamentous laxity. Vertebral anomalies, present in childhood, usually resolve with age, but osteoarthritis is progressive and severe. PSACH and EDM1 comprise a clinical spectrum with phenotypic overlap between mild forms of PSACH and EDM1 (summary by Briggs and Chapman, 2002). |
| Miscellaneouse | OMIM: waddling gait onset by age 2 years infants show normal size and appearance most patients need hip replacement by their mid-thirties the characteristic changes in the spine resolve by adolescence gonadal mosaicism may occur |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | N/A |
| Evidence | Weak |
| Gene symbol | COMP |
| Alias symbols | MED; EDM1; EPD1; PSACH; THBS5 |
| Gene name | cartilage oligomeric matrix protein |
| Gene map locus | 19p13.1; chr19:18,782,773-18,791,305(-) |
| Ensembl Gene ID | ENSG00000105664 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016] |
| Repeat unit | GAC |
| Normal repeat copies | 5 |
| Pathogenic repeat copies | ≥6 |
| Gene | COMP |
| Repeat location | CDS |
| Chromosome locus | chr19:18786032-18786049 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | A mismatch in a d(GAC)6·d(GAC)6 duplex induces negative supercoiling, leading to a local B-to-Z DNA transition. This transition facilitates the binding of d(GAC)7·d(GAC)7 with the Zα-binding domain of human adenosine deaminase acting on RNA 1 (ADAR1, hZαADAR1), as confirmed by CD, NMR, and microscale thermophoresis studies. The CD results indicated that hZαADAR1 recognizes the zigzag backbone of d(GAC)7·d(GAC)7 at the B-Z junction and subsequently converts it into Z-DNA via the so-called passive mechanism. Molecular dynamics simulations carried out for the modeled hZαADAR1-d(GAC)6d(GAC)6 complex confirmed the retention of previously reported important interactions between the two molecules. These findings suggest that hZαADAR1 binding with the GAC hairpin stem in COMP can lead to a non-genetic, RNA editing-mediated substitution in COMP that may then play a crucial role in the development of pseudoachondroplasia. [By PMID: 28924040] |
| Pathway annotation | Reactome, KEGG |
| PMID | 9887340 |
| Authors | Délot E, King LM, Briggs MD, Wilcox WR, Cohn DH |
| Title | Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene |
| Journal | Hum Mol Genet. 8(1):123-8 |
| Year | 1999 |