A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations
| Autor: | Eugen Boltshauser, A. Giedion, Eveliina Jakkula, M Marti, Luisa Bonafé, V Schuster, A Capone, Georg Eich, Andrea Superti-Furga, Jaana Lohiniva, Leena Ala-Kokko |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty DNA Mutational Analysis Cartilage Oligomeric Matrix Protein Osteochondrodysplasias medicine.disease_cause Short stature Bone and Bones Collagen Type IX Multiple epiphyseal dysplasia Molecular genetics Genetics medicine Humans Matrilin Proteins Genetic Predisposition to Disease Child Myopathy Genetics (clinical) Glycoproteins Cartilage oligomeric matrix protein Extracellular Matrix Proteins Mutation Thrombospondin Muscle Weakness biology medicine.disease Magnetic Resonance Imaging Molecular biology Pedigree Radiography Amino Acid Substitution biology.protein Female medicine.symptom Letter to JMG |
| Zdroj: | Journal of Medical Genetics. 40:942-948 |
| ISSN: | 1468-6244 |
| Popis: | Multiple epiphyseal dysplasia (MED) is clinically and genetically a heterogeneous disorder that affects growth centres and results in delayed and irregular mineralisation of the ossification centres.1,2 Recessively inherited MED (rMED; MIM 226900) accounts for a significant proportion of MED cases and is associated with mutations in the sulphate transporter gene, DTDST/SLC26A2.3,4 More often, MED is inherited as a dominant trait. Thus far, five different genes have been implicated in dominantly inherited MED: the gene for cartilage oligomeric matrix protein, COMP (MIM 600310); the genes for the α1, α2, and α3 chains of collagen IX, COL9A1 (MIM 120165), COL9A2 (MIM 120260), and COL9A3 (MIM 120270); and the gene for matrilin-3, MATN3 (MIM 602109). Patients with the severe forms of MED have short stature and major disability because of joint pain and stiffness. In the milder forms, height can be normal and joint complaints minimal. Mutations in COMP typically lead to the severe forms of dominant MED (MIM 132400) and can also cause a related but more severe disorder—pseudoachondroplasia (PSACH, MIM 177170). COMP is a pentameric extracellular glycoprotein that belongs to the thrombospondin protein family.5–7 It consists of a coiled coil N-terminal domain responsible for pentamerisation, four epidermal growth factor (EGF)-like repeats, eight thrombospondin type 3 (T3) repeats, and a large C-terminal globular domain. Mutations in COMP that cause MED are located in the T3 repeats.1,2 Mutations in these repeats alter the conformation of the protein and affect its ability to bind calcium.8–10 No mutations have been reported in the N-terminal domain or the EGF-like domains in MED. Only four mutations causing MED have been found in the C-terminal domain—two (T585R and T585M) in patients with unclassified MED,1,11 and the other two (R718W and N742fsX743) in patients with “severe MED” … |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|