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.

  • Letter
  • Published:

Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2

Abstract

Opitz syndrome (OS, McKusick 145410)1 is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome2, and G syndrome3. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity4. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports5,6 suggested that OS was inherited as an autosomal dominant trait7. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. McKusick, V.A. (1994) Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders. Eleventh Edition, 759–761 (Johns Hopkins University Press, Baltimore, 1994).

    Google Scholar 

  2. Opitz, J.M., Summitt, R.L. & Smith, D.W. The BBB syndrome familial telecanthus with associated congenital anomalies. Birth Defects: Original Article Series V(2), 86–94 (1969).

    Google Scholar 

  3. Opitz, J.M., Frías, J.L., Guttenberger, J.E. & Pellet, J.R. The G syndrome of multiple congenital anomalies. Birth Defects: Original Article Series V(2), 95–102 ((1969).

    Google Scholar 

  4. Cordero, J.F. & Holmes, L.B. Phenotypic overlap of the BBB and G syndromes. Am. J. med. Genet. 2, 145–152 (1978).

    Article  CAS  PubMed  Google Scholar 

  5. Fardon, P.A. & Donnai, D. Male to male transmission of the G syndrome. Clin. Genet. 24, 446–448 (1983).

    Article  Google Scholar 

  6. Stoll, C., Geraudel, A., Berland, H., Roth, M.-P. & Dott, B. Male to male transmission of the hypertelorism-hypospadias (BBB) syndrome. Am. J. med. Genet. 20, 221–225 (1978).

    Article  Google Scholar 

  7. Opitz, J.M. Editorial comment: G syndrome (hypertelorism with esopnageal abnormality and hypospadias, or hypospadias-dysphagia, or “Opitz-Frías” or “Opitz-G” syndrome) — perspective in 1987 and bibliography. Am. J. med. Genet. 28, 275–285 (1987).

    Article  CAS  PubMed  Google Scholar 

  8. Wittwer, B., Kircheisen, R., Leutelt, J. & Gal, A. Gene of a new X-linked syndrome with multiple congenital anomalies and severe mental retardation maps to Xp22–pter. Am. J. hum. Genet. 55(S), A1207 (1994).

    Google Scholar 

  9. Cohen Jr, M.M. Craniofrontonasal dysplasia. Birth Defects: Original Article Series XV(5B), 85–89 (1979).

    Google Scholar 

  10. MacPherson, E., Estop, A. & Paulus-Thomas, J. Craniofrontonasal dysplasia in a girl with del (X)(p22. 2). Am. J. hum. Genet. 49(S), A774 (1991).

    Google Scholar 

  11. Driscoll, D.A. et al. Deletions and microdeletions of 22q11 in velo-cardio-facial syndrome. Amer. J. med. Genet. 44, 261–268 (1992).

    Article  CAS  Google Scholar 

  12. Driscoll, D.A., Budarf, M.L. & Emanuel, B.S. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am. J. hum. Genet. 50, 924–933 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Goldmutz, E. et al. Microdeletions of chromosomal region b22q11.2 in patients with congenital conotruncal cardiac defects. J. med. Genet. 30, 807–812 (1993).

    Article  Google Scholar 

  14. Vortkamp, A., Gessler, M. & Grzeschik, K.-H. GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. Nature 352, 539–540 (1991).

    Article  CAS  PubMed  Google Scholar 

  15. Franzè, A., Archidiacono, N., Rocchi, M., Marino, M. & Grimaldi, G. Isolation and expression analysis of a human zinc finger gene (ZFN41) located on the short arm of the X chromosome. Genomics 7, 728–736 (1991).

    Article  Google Scholar 

  16. Marino, M. et al. A novel member of the human zinc finger protein gene family: isolation, mapping, and expression. Mammal. Genet. 4, 252–257 (1993).

    Article  CAS  Google Scholar 

  17. Page, D.C. et al. Chromosomal localization of ZFX-a human gene that escapes X-inactivation-and its murine homologs. Genomics 7, 37–46 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Aubry, M. et al. Cloning of six new genes with zinc finger motifs mapping to the short and long arms of human acrocentric chromosome 22 (p and q11.2). Genomics 13, 641–648 (1992).

    Article  CAS  PubMed  Google Scholar 

  19. Allanson, J.E. G syndrome: an unusual family. Am. J. med. Genet. 31, 637–642 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Brooks, J.K., Leonard, C.O. & Coccaro, P.J. Opitz (BBB/G) syndrome: oral manifestations. Am. J. med. Genet. 43, 595–601 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Guion-Almeida, M.L. & Richieri-Costa, A. CMS midline anomalies in the Opitz G/BBB syndrome: report on 12 Brazilian patients. Am. J. med. Genet. 43, 918–928 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. 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 

  23. Ott, J. Analysis of Human Genetic Linkage. (Johns Hopkins Press, Baltimore, 1992).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robin, N., Feldman, G., Aronson, A. et al. Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2. Nat Genet 11, 459–461 (1995). https://doi.org/10.1038/ng1295-459

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1295-459

This article is cited by

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