Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis

Nature Genetics volume 3, pages 338–341 (1993)Cite this article

Abstract

Cartilage-hair hypoplasia (CHH) is an autosomal recessive skeletal dysplasia of unknown pathogenesis leading to short-limbed stature. Associated features include hypoplasia of hair, abnormal cellular immunity, deficient erythrogenesis, increased risk of malignancies, Hirschsprung disease, and Diamond-Blackfan type hypoplastic anaemia. We mapped the CHH gene by linkage analysis with 5 markers to chromosome 9. Multipoint linkage analysis gives a lod score of 9.94 for a location between D9S43 and D9S50. Based on strong linkage disequilibrium the closest marker, D9S50, is likely to be less than 1 cM from the gene. No heterogeneity was observed in 14 Finnish families, nor was there evidence of reduced penetrance. These results provide a starting point for the eventual cloning and characterization of the CHH gene.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. McKusick, V.A. Mendelian Inheritance in Man 9th edn (Johns Hopkins University Press, Baltimore, 1991).

    Google Scholar 

  2. McKusick, V.A., Eldridge, R., Hostetler, J.A., Ruangwit, U. & Egeland, J.A. Dwarfism in the Amish II. Cartilage-hair hypoplasia. Bull. Johns Hopkins Hosp. 116, 232–272 (1965).

    Google Scholar 

  3. Polmar, S.H. & Pierce, G.F. Cartilage hair hypoplasia: Immunological aspects and their clinical implications. Clin. Immunol. Immunopathol. 40, 87–93 (1986).

    Article  CAS  Google Scholar 

  4. Francomano, C.A., Trojak, J.E. & McKusick, V.A. Cartilage hair hypoplasia in the Amish: Increased susceptibility to malignancy. Am. J. hum. Genet. 35, 89A (1983).

    Google Scholar 

  5. Mäkitie, O. & Kaitila, I. Cartilage-hair hypoplasia — Clinical manifestations in 108 Finnish patients. Eur. J. Pediatr. (in the press).

  6. Perheentupa, J. Kolme periytyvää kasvuhälriötä. (in Finnish) Duodecim 88, 60–71 (1972).

    CAS  PubMed  Google Scholar 

  7. Mäkitie, O. Cartilage-hair hypoplasia. Clinical, radiological and genetic study of an inherited skeletal dysplasia (thesis, University of Helsinki, 1992).

    Google Scholar 

  8. Mäkitie, O. Cartilage-hair hypoplasia in Finland — epidemiological and genetic aspects of 107 patients. J. med. Genet. 29, 652–655 (1992).

    Article  Google Scholar 

  9. Weber, J.L. & May, P.E. Dinucleotide repeat polymorphism at the D9S43 locus. Nucl. Acids Res. 18, 2203 (1991).

    Google Scholar 

  10. Wilkie, P.J., Krizman, D.B. & Weber, J.L. Linkage map of human chromosome 9 microsatellite polymorphisms. Genomics 12, 607–609 (1992).

    Article  CAS  Google Scholar 

  11. Fujita, R., Hanauer, A., Sirugo, G., Heilig, R. & Mandel, J.-L. Additional polymorphisms at marker loci D9S5 and D9S15 generate extended haplotypes in linkage disequilibrium with Friedreich ataxia. Proc. natn. Acad. Sci. U.S.A. 87, 1796–1800 (1990).

    Article  CAS  Google Scholar 

  12. Povey, S., Falk, C. & Smith, M. Report of the committee on the genetic constitution of chromosome 9. Cytogenet. Cell Genet. 58, 403–427 (1991).

    Article  Google Scholar 

  13. Edwards, J.H. In Population Structure and Genetic Disorders (eds Eriksson A.W., Forsius H.R., Nevanlinna H.R., Workman P.L. & Norio R.K.) 239–255 (Academic Press, London, 1980).

    Google Scholar 

  14. NIH/CEPH Collaborative Mapping Group. A comprehensive genetic linkage map of the human genome. Science 258, 67–86 (1992).

  15. Shaw, J., Lichter, P., Driesel, A.J., Williamson, R. & Chamberlain, S. Regional mapping of the Friedreich ataxia locus to human chromosome 9q13 → q21.1. Cytogenet. Cell Genet. 53, 221–224 (1990).

    Article  CAS  Google Scholar 

  16. Pierce, G.F. & Polmar, S.H. Lymphocyte dysfunction in cartilage-hair hypoplasia: Evidence for an intrinsic defect in cellular proliferation. J. Immunol. 129, 570–575 (1982).

    CAS  PubMed  Google Scholar 

  17. Mäkitie, O., Rajantie, J. & Kaitila, I. Anaemia and macrocytosis - unrecognized features in cartilage-hair hypoplasia. Acta Paediatr. (in the press).

  18. Fountain, J.W. et al. Genetic and physical map of the interferon region on chromosome 9p. Genomics 14, 105–112 (1992).

    Article  CAS  Google Scholar 

  19. Trent, J.M., Olson, S. & Lawn, R.M. Chromosomal localization of human leukocyte, fibroblast, and immune interferon genes by means of in situ hybridization. Proc. natn. Acad. Sci. U.S.A. 79, 7809–7813 (1982).

    Article  CAS  Google Scholar 

  20. Olopade, O.I. et al. Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics 14, 437–443 (1992).

    Article  CAS  Google Scholar 

  21. Anderson, M.A. & Gusella, J.F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In vitro 20, 856–858 (1984).

    Article  CAS  Google Scholar 

  22. Kunkel, L.M. et al. Analysis of human Y-chromosome -specific reiterated DNA in chromosome variants. Proc. natn. Acad. Sci. U.S.A. 74, 1245–1249 (1977).

    Article  CAS  Google Scholar 

  23. Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 51, 319–337 (1987).

    Article  CAS  Google Scholar 

  24. Hästbacka, J., Kaitila, I., Sistonen, P. & de la Chapelle, A. Diastrophic dysplasia gene maps to the distal long arm of chromosome 5. Proc. natn. Acad. Sci. U.S.A. 87, 8056–8059 (1990).

    Article  Google Scholar 

  25. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Genetics, University of Helsinki, 00290, Helsinki, Finland

    Tuija Sulisalo, Johanna Hästbacka, Albert de la Chapelle & Ilkka Kaitila

  2. Finnish Red Cross Blood Transfusion Service, 00310, Helsinki, Finland

    Pertti Sistonen

  3. Department of Clinical Genetics, University Hospital of Uppsala, 75185, Uppsala, Sweden

    Claes Wadelius

  4. Department of Medical Genetics, Helsinki University Central Hospital, 00290, Helsinki, Finland

    Outi Mäkitie & Ilkka Kaitila

  5. Children's Hospital, Helsinki University Central Hospital, 00290, Helsinki, Finland

    Outi Mäkitie

Authors
  1. Tuija Sulisalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pertti Sistonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Johanna Hästbacka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claes Wadelius
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Outi Mäkitie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Albert de la Chapelle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ilkka Kaitila
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sulisalo, T., Sistonen, P., Hästbacka, J. et al. Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis. Nat Genet 3, 338–341 (1993). https://doi.org/10.1038/ng0493-338

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0493-338

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing