title: Comprehensive screening of multiple epiphyseal dysplasia mutations in Japanese population.
abstract: Multiple epiphyseal dysplasia (MED) is among the most genetically heterogeneous skeletal dysplasias. Six genes involved in MED, COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST have been identified; however, the presence of additional disease genes has been reported, and the detection rate for mutations in known genes accounts for no more than 50% of patients with MED in Western populations. Here, we screened the six known disease genes in 35 consecutive Japanese MED patients. We analyzed the entire coding region of each gene, along with flanking intron-exon junctions, by direct sequencing. A total of 19 mutations were identified in COMP, MATN3, COL9A2, COL9A3, and DTDST. The detection rate for known mutations was higher in this study than in previous reports, and we identified a substantially different spectrum of mutations. Mutations in MATN3 were more prevalent among these Japanese patients, whereas no DTDST mutations were detected. Most of the mutations were localized within specific regions of each gene: COMP mutations were found in the calmodulin-like repeat domains; MATN3 mutations in the von Willebrand factor type A domain; and type IX collagen gene mutations occurred in the third collagenous domains. Based on the integration of clinical and genetic information, we propose an algorithm for detecting mutations in Japanese MED patients. Our study further supports the existence of additional MED gene(s).
authors.affiliation: Center for Molecular Biology and Cytogenetics, SRL Inc., Hino, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Itoh
authors.forename: Shuya
authors.initials: S
authors.lastname: Shirahama
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakashima
authors.forename: Koichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Haga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitoh
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D001483:Base Sequence; D064236:Cartilage Oligomeric Matrix Protein; D024081:Collagen Type IX / Q000235:genetics; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005820:Genetic Testing; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007438:Introns; D007564:Japan / Q000453:epidemiology; D064235:Matrilin Proteins; D017720:Molecular Epidemiology / Q000379:methods*; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D019914:Taq Polymerase / Q000032:analysis
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D019914:Taq Polymerase