Revisit of multiple epiphyseal dysplasia: Ethnic difference in genotypes and comparison of radiographic features linked to the COMP and MATN3 genes

Ok Hwa Kim, Hyunwoong Park, Moon Woo Seong, Tae Joon Cho, Gen Nishimura, Andrea Superti-Furga, Sheila Unger, Shiro Ikegawa, In Ho Choi, Hae Ryong Song, Hyun Woo Kim, Won Joon Yoo, Jong Sup Shim, Chin Youb Chung, Chang Wug Oh, Changhoon Jeong, Kwang Soon Song, Sang Gyo Seo, Sung Im Cho, Im Kyung YeoSo Yeon Kim, Seungman Park, Sung Sup Park

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13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2669-2680
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number11
DOIs
Publication statusPublished - 2011 Nov 1

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Keywords

  • COMP
  • MATN3
  • Multiple epiphyseal dysplasia
  • Radiologic phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kim, O. H., Park, H., Seong, M. W., Cho, T. J., Nishimura, G., Superti-Furga, A., Unger, S., Ikegawa, S., Choi, I. H., Song, H. R., Kim, H. W., Yoo, W. J., Shim, J. S., Chung, C. Y., Oh, C. W., Jeong, C., Song, K. S., Seo, S. G., Cho, S. I., ... Park, S. S. (2011). Revisit of multiple epiphyseal dysplasia: Ethnic difference in genotypes and comparison of radiographic features linked to the COMP and MATN3 genes. American Journal of Medical Genetics, Part A, 155(11), 2669-2680. https://doi.org/10.1002/ajmg.a.34246