Human Genetics

, Volume 103, Issue 6, pp 633–638

Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia

  • S. Ikegawa
  • Hirofumi Ohashi
  • Gen Nishimura
  • Kyoung Chang Kim
  • Akio Sannohe
  • Mamori Kimizuka
  • Yoshimitsu Fukushima
  • Toshiro Nagai
  • Yusuke Nakamura
Original investigation

DOI: 10.1007/s004390050883

Cite this article as:
Ikegawa, S., Ohashi, H., Nishimura, G. et al. Hum Genet (1998) 103: 633. doi:10.1007/s004390050883

Abstract

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are common skeletal dysplasias with impaired enchondral ossification and premature degenerative joint disease. The two disorders were in the past considered to be distinct clinical entities; however, recent studies have proven that both diseases can result from mutations of the gene encoding cartilage oligomeric matrix protein (COMP). To characterize further COMP mutations and investigate phenotype-genotype relationships, we screened this gene in 15 patients with PSACH or MED by directly sequencing polymerase chain reaction products from genomic DNA. We identified ten mutations involving conserved residues among the eight calmodulin-like repeats of the gene product: seven were novel missense mutations in exons 9, 10, 11, 13 or 14, and the other three resulted from deletion of one of the five GAC repeats in exon 13. We have found that the GAC repeats in the 7th calmodulin-like repeat in exon 13 represent a hot-spot for mutation, and that mutations in the 7th calmodulin-like repeat produce severe PSACH phenotypes while mutations elsewhere in the gene exhibit mild PSACH or MED phenotypes. These genotype-phenotype correlations may facilitate molecular diagnosis and classification of PSACH and MED, and provide insight into the relationship between structure and function of the COMP gene product.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • S. Ikegawa
    • 1
  • Hirofumi Ohashi
    • 2
  • Gen Nishimura
    • 3
  • Kyoung Chang Kim
    • 2
  • Akio Sannohe
    • 4
  • Mamori Kimizuka
    • 5
  • Yoshimitsu Fukushima
    • 6
  • Toshiro Nagai
    • 7
  • Yusuke Nakamura
    • 1
  1. 1.Laboratory of Genome Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan e-mail: sikegawa@ims.u-tokyo.ac.jp, Tel: +81-3-5449-5233, Fax: +81-3-5449-5406JP
  2. 2.Division of Medical Genetics, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-shi, Saitama 339, JapanJP
  3. 3.Department of Radiology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga-gun, Tochigi, 321-02, JapanJP
  4. 4.Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital, 1-1-2 Higashitsukurimichi Aomori-shi, Aomori 030, JapanJP
  5. 5.Department of Orthopaedics, National Rehabilitation Center for Disabled Children, 1-1-10 Komone, Iatabashi-ku, Tokyo 173, JapanJP
  6. 6.Department of Hygiene and Medical Genetics, Shinsyu University School of Medicine, 3-1-1 Asahi, Matsumoto-shi, Nagano 390, JapanJP
  7. 7.Department of Pediatrics, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minamikoshigaya-shi, Saitama 343, JapanJP