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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Apr;89(4):1344–1349. doi: 10.1172/JCI115720

Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms.

C Larsson 1, J Shepherd 1, Y Nakamura 1, C Blomberg 1, G Weber 1, B Werelius 1, N Hayward 1, B Teh 1, T Tokino 1, B Seizinger 1
PMCID: PMC442996  PMID: 1348254

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited predisposition to neoplastic lesions of the parathyroids, pancreas, and the pituitary. We have previously located the predisposing genetic defect to the long arm of chromosome 11 by genetic linkage. In this study, 124 members of six MEN1 families, including 59 affected individuals, were genotyped for restriction fragment length polymorphisms with different DNA probes, and the genetic linkage between these marker systems and MEN1 was determined. 13 marker systems (17 DNA probes) were found to be linked to MEN1. These markers are located within a region on chromosome 11 spanning 14% meiotic recombinations, with the MEN1 locus in the middle. Four of the marker systems are on the centromeric side of MEN1, and four on the telomeric side, based on meiotic crossovers. The remaining five DNA probes are closely linked to MEN1, with no crossovers in our set of families. The 13 marker systems can be used for an accurate and reliable premorbid test for MEN1. In most clinical situations it is possible to identify a haplotype of this part of chromosome 11 with the mutant MEN1 allele in the middle. The calculated predictive accuracy is greater than 99.5% if three such marker systems are informative. Therefore, genetic linkage testing can be used for informed genetic counseling in MEN1 families, and to avoid unnecessary biochemical screening programs.

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Selected References

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

  1. Brandi M. L., Marx S. J., Aurbach G. D., Fitzpatrick L. A. Familial multiple endocrine neoplasia type I: a new look at pathophysiology. Endocr Rev. 1987 Nov;8(4):391–405. doi: 10.1210/edrv-8-4-391. [DOI] [PubMed] [Google Scholar]
  2. Byström C., Larsson C., Blomberg C., Sandelin K., Falkmer U., Skogseid B., Oberg K., Werner S., Nordenskjöld M. Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1968–1972. doi: 10.1073/pnas.87.5.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Friedman E., Sakaguchi K., Bale A. E., Falchetti A., Streeten E., Zimering M. B., Weinstein L. S., McBride W. O., Nakamura Y., Brandi M. L. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N Engl J Med. 1989 Jul 27;321(4):213–218. doi: 10.1056/NEJM198907273210402. [DOI] [PubMed] [Google Scholar]
  4. Fujiwara S., Fisher R. J., Seth A., Bhat N. K., Showalter S. D., Zweig M., Papas T. S. Characterization and localization of the products of the human homologs of the v-ets oncogene. Oncogene. 1988 Feb;2(2):99–103. [PubMed] [Google Scholar]
  5. Janson M., Larsson C., Werelius B., Jones C., Glaser T., Nakamura Y., Jones C. P., Nordenskjöld M. Detailed physical map of human chromosomal region 11q12-13 shows high meiotic recombination rate around the MEN1 locus. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10609–10613. doi: 10.1073/pnas.88.23.10609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Julier C., Nakamura Y., Lathrop M., O'Connell P., Leppert M., Litt M., Mohandas T., Lalouel J. M., White R. A detailed genetic map of the long arm of chromosome 11. Genomics. 1990 Jul;7(3):335–345. doi: 10.1016/0888-7543(90)90167-s. [DOI] [PubMed] [Google Scholar]
  7. Kidd K. K., Bowcock A. M., Schmidtke J., Track R. K., Ricciuti F., Hutchings G., Bale A., Pearson P., Willard H. F., Gelernter J. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet. 1989;51(1-4):622–947. doi: 10.1159/000132810. [DOI] [PubMed] [Google Scholar]
  8. Knudson A. G., Jr Retinoblastoma: a prototypic hereditary neoplasm. Semin Oncol. 1978 Mar;5(1):57–60. [PubMed] [Google Scholar]
  9. Larsson C., Skogseid B., Oberg K., Nakamura Y., Nordenskjöld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988 Mar 3;332(6159):85–87. doi: 10.1038/332085a0. [DOI] [PubMed] [Google Scholar]
  10. Nakamura Y., Larsson C., Julier C., Byström C., Skogseid B., Wells S., Oberg K., Carlson M., Taggart T., O'Connell P. Localization of the genetic defect in multiple endocrine neoplasia type 1 within a small region of chromosome 11. Am J Hum Genet. 1989 May;44(5):751–755. [PMC free article] [PubMed] [Google Scholar]
  11. Shepherd J. J. Latent familial multiple endocrine neoplasia in Tasmania. Med J Aust. 1985 Apr 1;142(7):395–397. doi: 10.5694/j.1326-5377.1985.tb133152.x. [DOI] [PubMed] [Google Scholar]
  12. Skogseid B., Eriksson B., Lundqvist G., Lörelius L. E., Rastad J., Wide L., Akerström G., Oberg K. Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab. 1991 Aug;73(2):281–287. doi: 10.1210/jcem-73-2-281. [DOI] [PubMed] [Google Scholar]
  13. Teh B. T., Hayward N. K., Wilkinson S., Woods G. M., Cameron D., Shepherd J. J. Clonal loss of INT-2 alleles in sporadic and familial pancreatic endocrine tumours. Br J Cancer. 1990 Aug;62(2):253–254. doi: 10.1038/bjc.1990.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Thakker R. V., Bouloux P., Wooding C., Chotai K., Broad P. M., Spurr N. K., Besser G. M., O'Riordan J. L. Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med. 1989 Jul 27;321(4):218–224. doi: 10.1056/NEJM198907273210403. [DOI] [PubMed] [Google Scholar]
  15. Tokino T., Takahashi E., Mori M., Tanigami A., Glaser T., Park J. W., Jones C., Hori T., Nakamura Y. Isolation and mapping of 62 new RFLP markers on human chromosome 11. Am J Hum Genet. 1991 Feb;48(2):258–268. [PMC free article] [PubMed] [Google Scholar]
  16. WERMER P. ENDOCRINE ADENOMATOSIS AND PEPTIC ULCER IN A LARGE KINDRED. INHERITED MULTIPLE TUMORS AND MOSAIC PLEIOTROPISM IN MAN. Am J Med. 1963 Aug;35:205–212. doi: 10.1016/0002-9343(63)90212-2. [DOI] [PubMed] [Google Scholar]
  17. Williamson R., Bowcock A., Kidd K., Pearson P., Schmidtke J., Chan H. S., Chipperfield M., Cooper D. N., Hewitt J., Lewitter F. Report of the DNA committee and catalogues of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet. 1990;55(1-4):457–778. doi: 10.1159/000133027. [DOI] [PubMed] [Google Scholar]

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