title: COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia.
abstract: The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making.
authors.affiliation: National Genetics Reference Laboratory (Manchester), Regional Genetics Services, St. Mary's Hospital, Manchester, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Kennedy
authors.forename: Gail
authors.initials: G
authors.lastname: Jackson
authors.forename: Simon
authors.initials: S
authors.lastname: Ramsden
authors.forename: Jacky
authors.initials: J
authors.lastname: Taylor
authors.forename: William
authors.initials: W
authors.lastname: Newman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: Rob
authors.initials: R
authors.lastname: Elles
authors.forename: Michael D
authors.initials: MD
authors.lastname: Briggs
mesh_terms: D000293:Adolescent; D064236:Cartilage Oligomeric Matrix Protein; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D064235:Matrilin Proteins; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human