title: Revisit of multiple epiphyseal dysplasia: ethnic difference in genotypes and comparison of radiographic features linked to the COMP and MATN3 genes.
abstract: Multiple epiphyseal dysplasia (MED) is a genetically heterogeneous group of diseases characterized by variable degrees of epiphyseal abnormality primarily involving the hip and knee joints. The purpose of this study was to investigate the frequency of mutations in individuals with a clinical and radiographic diagnosis of MED and to test the hypothesis that characteristic radiological findings may be helpful in predicting the gene responsible. The radiographs of 74 Korean patients were evaluated by a panel of skeletal dysplasia experts. Six genes known to be associated with MED (COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST) were screened by sequencing. Mutations were found in 55 of the 63 patients (87%). MATN3 mutations were found in 30 patients (55%), followed by COMP mutations in 23 (41%), and COL9A2 and DTDST mutations in one patient (2%) each. Comparisons of radiographic findings in patients with COMP and MATN3 mutations showed that albeit marked abnormalities in hip and knee joints were observed in both groups, the degree of involvement and the morphology of dysplastic epiphyses differed markedly. The contour of the pelvic acetabulum, the presence of metaphyseal vertical striations, and/or the brachydactyly of the hand were also found to be highly correlated with the genotypes. The study confirms that MATN3 and COMP are the genes most frequently responsible for MED and that subtle radiographic signs may give precious indications on which gene(s) should be prioritized for mutational screening in a given individual.
authors.affiliation: Department of Radiology, Ajou University Hospital, Suwon, Korea.
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kim
authors.forename: Hyunwoong
authors.initials: H
authors.lastname: Park
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: In Ho
authors.initials: IH
authors.lastname: Choi
authors.forename: Hae-Ryong
authors.initials: HR
authors.lastname: Song
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Won Joon
authors.initials: WJ
authors.lastname: Yoo
authors.forename: Jong Sup
authors.initials: JS
authors.lastname: Shim
authors.forename: Chin Youb
authors.initials: CY
authors.lastname: Chung
authors.forename: Chang-Wug
authors.initials: CW
authors.lastname: Oh
authors.forename: Changhoon
authors.initials: C
authors.lastname: Jeong
authors.forename: Kwang Soon
authors.initials: KS
authors.lastname: Song
authors.forename: Sang Gyo
authors.initials: SG
authors.lastname: Seo
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.forename: Im Kyung
authors.initials: IK
authors.lastname: Yeo
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Seungman
authors.initials: S
authors.lastname: Park
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024081:Collagen Type IX / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D015894:Genome, Human; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D008297:Male; D064235:Matrilin Proteins; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D017384:Sequence Deletion; D012720:Severity of Illness Index; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D027321:Anion Transport Proteins; C439970:COL9A1 protein, human; D064236:Cartilage Oligomeric Matrix Protein; D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters; C577553:TSP5 protein, human