Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1998 Dec;63(6):1659–1662. doi: 10.1086/302158

Mutation of the type X collagen gene (COL10A1) causes spondylometaphyseal dysplasia.

S Ikegawa 1, G Nishimura 1, T Nagai 1, T Hasegawa 1, H Ohashi 1, Y Nakamura 1
PMCID: PMC1377637  PMID: 9837818

Abstract

Spondylometaphyseal dysplasia (SMD) comprises a heterogeneous group of heritable skeletal dysplasias characterized by modifications of the vertebral bodies of the spine and metaphyses of the tubular bones. The genetic etiology of SMD is currently unknown; however, the type X collagen gene (COL10A1) is considered an excellent candidate, for two reasons: first, Schmid metaphyseal chondrodysplasia, a condition known to result from COL10A1 mutations, shows a significant phenotypic overlap with SMD; and, second, transgenic mice carrying deletions in type X collagen show SMD phenotypes. Hence, we examined the entire coding region of COL10A1 by direct sequencing of DNA from five unrelated patients with SMD and found a heterozygous missense mutation (Gly595Glu) cosegregating with the disease phenotype in one SMD family. This initial documented identification of a mutation in SMD expands our knowledge concerning the range of the pathological phenotypes that can be produced by aberrations of type X collagen (type X collagenopathy).

Full Text

The Full Text of this article is available as a PDF (318.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonaventure J., Rousseau F., Legeai-Mallet L., Le Merrer M., Munnich A., Maroteaux P. Common mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism. Am J Med Genet. 1996 May 3;63(1):148–154. doi: 10.1002/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  2. Brass A., Kadler K. E., Thomas J. T., Grant M. E., Boot-Handford R. P. The fibrillar collagens, collagen VIII, collagen X and the C1q complement proteins share a similar domain in their C-terminal non-collagenous regions. FEBS Lett. 1992 Jun 1;303(2-3):126–128. doi: 10.1016/0014-5793(92)80503-9. [DOI] [PubMed] [Google Scholar]
  3. Hasegawa T., Kozlowski K., Nishimura G., Hara H., Hasegawa Y., Aso T., Koto S., Nagai T., Tsuchiya Y. Japanese type of spondylo-metaphyseal dysplasia. Pediatr Radiol. 1994;24(3):194–197. doi: 10.1007/BF02012189. [DOI] [PubMed] [Google Scholar]
  4. Ikegawa S., Nakamura K., Nagano A., Haga N., Nakamura Y. Mutations in the N-terminal globular domain of the type X collagen gene (COL10A1) in patients with Schmid metaphyseal chondrodysplasia. Hum Mutat. 1997;9(2):131–135. doi: 10.1002/(SICI)1098-1004(1997)9:2<131::AID-HUMU5>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  5. Jacenko O., LuValle P. A., Olsen B. R. Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition. Nature. 1993 Sep 2;365(6441):56–61. doi: 10.1038/365056a0. [DOI] [PubMed] [Google Scholar]
  6. Kirsch T., von der Mark K. Isolation of human type X collagen and immunolocalization in fetal human cartilage. Eur J Biochem. 1991 Mar 28;196(3):575–580. doi: 10.1111/j.1432-1033.1991.tb15852.x. [DOI] [PubMed] [Google Scholar]
  7. Kuivaniemi H., Tromp G., Prockop D. J. Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat. 1997;9(4):300–315. doi: 10.1002/(SICI)1098-1004(1997)9:4<300::AID-HUMU2>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  8. Lachman R. S., Rimoin D. L., Spranger J. Metaphyseal chondrodysplasia, Schmid type. Clinical and radiographic delineation with a review of the literature. Pediatr Radiol. 1988;18(2):93–102. doi: 10.1007/BF02387549. [DOI] [PubMed] [Google Scholar]
  9. Maroteaux P., Spranger J. The spondylometaphyseal dysplasias. A tentative classification. Pediatr Radiol. 1991;21(4):293–297. doi: 10.1007/BF02018629. [DOI] [PubMed] [Google Scholar]
  10. Schmid T. M., Linsenmayer T. F. Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues. J Cell Biol. 1985 Feb;100(2):598–605. doi: 10.1083/jcb.100.2.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Spranger J., Winterpacht A., Zabel B. The type II collagenopathies: a spectrum of chondrodysplasias. Eur J Pediatr. 1994 Feb;153(2):56–65. doi: 10.1007/BF01959208. [DOI] [PubMed] [Google Scholar]
  12. Thomas J. T., Cresswell C. J., Rash B., Nicolai H., Jones T., Solomon E., Grant M. E., Boot-Handford R. P. The human collagen X gene. Complete primary translated sequence and chromosomal localization. Biochem J. 1991 Dec 15;280(Pt 3):617–623. doi: 10.1042/bj2800617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wallis G. A., Rash B., Sykes B., Bonaventure J., Maroteaux P., Zabel B., Wynne-Davies R., Grant M. E., Boot-Handford R. P. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet. 1996 Jun;33(6):450–457. doi: 10.1136/jmg.33.6.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Warman M. L., Abbott M., Apte S. S., Hefferon T., McIntosh I., Cohn D. H., Hecht J. T., Olsen B. R., Francomano C. A. A type X collagen mutation causes Schmid metaphyseal chondrodysplasia. Nat Genet. 1993 Sep;5(1):79–82. doi: 10.1038/ng0993-79. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES