Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1989 Nov;45(5):681–688.

Genetic linkage analysis of hereditary arthro-ophthalmopathy (Stickler syndrome) and the type II procollagen gene.

R G Knowlton 1, E J Weaver 1, A F Struyk 1, W H Knobloch 1, R A King 1, K Norris 1, A Shamban 1, J Uitto 1, S A Jimenez 1, D J Prockop 1
PMCID: PMC1683441  PMID: 2573273

Abstract

Hereditary arthro-ophthalmopathy (AO), or Stickler syndrome, is a dominantly inherited disorder characterized by vitreo-retinal degeneration and frequently accompanied by epiphyseal dysplasia and premature degenerative joint disease. Three large families with AO were analyzed for clinical manifestations of the disease and for coinheritance of the genetic defect with RFLPs in the type II procollagen gene (COL2A1). Genetic linkage between AO and COL2A1 was demonstrated in the largest family, with a maximum LOD score of 3.52 at a recombination distance of zero. Data from a second family also supported linkage of AO and COL2A1, with a LOD score of 1.20 at a recombination distance of zero. These results are consistent with the conclusion that mutations in the COL2A1 gene are responsible for AO in these two families. In a third AO family, however, recombination between AO and COL2A1 occurred in at least one meiosis, and the data were inconclusive with respect to linkage.

Full text

PDF
681

Images in this article

Selected References

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

  1. Balazs I., Purrello M., Alhadeff B., Grzeschik K. H., Szabo P. Isolation and subregional mapping of a human cDNA clone detecting a common RFLP on chromosome 12. Hum Genet. 1984;68(1):57–61. doi: 10.1007/BF00293873. [DOI] [PubMed] [Google Scholar]
  2. Barker D., McCoy M., Weinberg R., Goldfarb M., Wigler M., Burt R., Gardner E., White R. A test of the role of two oncogenes in inherited predisposition to colon cancer. Mol Biol Med. 1983 Sep;1(2):199–206. [PubMed] [Google Scholar]
  3. Beighton P., de Paepe A., Danks D., Finidori G., Gedde-Dahl T., Goodman R., Hall J. G., Hollister D. W., Horton W., McKusick V. A. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581–594. doi: 10.1002/ajmg.1320290316. [DOI] [PubMed] [Google Scholar]
  4. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blair N. P., Albert D. M., Liberfarb R. M., Hirose T. Hereditary progressive arthro-ophthalmopathy of Stickler. Am J Ophthalmol. 1979 Nov;88(5):876–888. doi: 10.1016/0002-9394(79)90566-x. [DOI] [PubMed] [Google Scholar]
  6. Buroker N. E., Magenis R. E., Weliky K., Bruns G., Litt M. Four restriction fragment length polymorphisms revealed by probes from a single cosmid map to human chromosome 12q. Hum Genet. 1986 Jan;72(1):86–94. doi: 10.1007/BF00278825. [DOI] [PubMed] [Google Scholar]
  7. Conneally P. M., Edwards J. H., Kidd K. K., Lalouel J. M., Morton N. E., Ott J., White R. Report of the Committee on Methods of Linkage Analysis and Reporting. Cytogenet Cell Genet. 1985;40(1-4):356–359. doi: 10.1159/000132186. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Francomano C. A., Liberfarb R. M., Hirose T., Maumenee I. H., Streeten E. A., Meyers D. A., Pyeritz R. E. The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. Genomics. 1987 Dec;1(4):293–296. doi: 10.1016/0888-7543(87)90027-9. [DOI] [PubMed] [Google Scholar]
  10. Herrmann J., France T. D., Spranger J. W., Opitz J. M., Wiffler C. The Stickler syndrome (hereditary arthroophthalmopathy). Birth Defects Orig Artic Ser. 1975;11(2):76–103. [PubMed] [Google Scholar]
  11. Knobloch W. H. Inherited hyaloideoretinopathy and skeletal dysplasia. Trans Am Ophthalmol Soc. 1975;73:417–451. [PMC free article] [PubMed] [Google Scholar]
  12. Knobloch W. H., Layer J. M. Clefting syndromes associated with retinal detachment. Am J Ophthalmol. 1972 Apr;73(4):517–530. doi: 10.1016/0002-9394(72)90003-7. [DOI] [PubMed] [Google Scholar]
  13. Knowlton R. G., Brown V. A., Braman J. C., Barker D., Schumm J. W., Murray C., Takvorian T., Ritz J., Donis-Keller H. Use of highly polymorphic DNA probes for genotypic analysis following bone marrow transplantation. Blood. 1986 Aug;68(2):378–385. [PubMed] [Google Scholar]
  14. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liberfarb R. M., Hirose T., Holmes L. B. The Wagner-Stickler syndrome: a study of 22 families. J Pediatr. 1981 Sep;99(3):394–399. doi: 10.1016/s0022-3476(81)80324-1. [DOI] [PubMed] [Google Scholar]
  16. Litt M., White R. L. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. doi: 10.1073/pnas.82.18.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nakamura Y., Ballard L., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence pYNH15 on chromosome 12q [D12S17]. Nucleic Acids Res. 1988 Jan 25;16(2):779–779. doi: 10.1093/nar/16.2.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nunez A. M., Francomano C., Young M. F., Martin G. R., Yamada Y. Isolation and partial characterization of genomic clones coding for a human pro-alpha 1 (II) collagen chain and demonstration of restriction fragment length polymorphism at the 3' end of the gene. Biochemistry. 1985 Nov 5;24(23):6343–6348. doi: 10.1021/bi00344a004. [DOI] [PubMed] [Google Scholar]
  19. O'Connell P., Lathrop G. M., Law M., Leppert M., Nakamura Y., Hoff M., Kumlin E., Thomas W., Elsner T., Ballard L. A primary genetic linkage map for human chromosome 12. Genomics. 1987 Sep;1(1):93–102. doi: 10.1016/0888-7543(87)90110-8. [DOI] [PubMed] [Google Scholar]
  20. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  21. Prockop D. J., Kivirikko K. I. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376–386. doi: 10.1056/NEJM198408093110606. [DOI] [PubMed] [Google Scholar]
  22. STICKLER G. B., BELAU P. G., FARRELL F. J., JONES J. D., PUGH D. G., STEINBERG A. G., WARD L. E. HEREDITARY PROGRESSIVE ARTHRO-OPHTHALMOPATHY. Mayo Clin Proc. 1965 Jun;40:433–455. [PubMed] [Google Scholar]
  23. Sangiorgi F. O., Benson-Chanda V., de Wet W. J., Sobel M. E., Tsipouras P., Ramirez F. Isolation and partial characterization of the entire human pro alpha 1(II) collagen gene. Nucleic Acids Res. 1985 Apr 11;13(7):2207–2225. doi: 10.1093/nar/13.7.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stoker N. G., Cheah K. S., Griffin J. R., Pope F. M., Solomon E. A highly polymorphic region 3' to the human type II collagen gene. Nucleic Acids Res. 1985 Jul 11;13(13):4613–4622. doi: 10.1093/nar/13.13.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Temple I. K. Stickler's syndrome. J Med Genet. 1989 Feb;26(2):119–126. doi: 10.1136/jmg.26.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES