Advertisement

Journal of Endocrinological Investigation

, Volume 24, Issue 10, pp 806–810 | Cite as

Multiple endocrine neoplasia type 1Burin from Mauritius: A novel MEN 1 mutation1

  • C. Kong
  • S. Ellard
  • C. Johnston
  • Nadir R. Farid
Case Report

Abstract

We describe a kindred from Mauritius with an incomplete variant of multiple endocrine neoplasia type 1 (MEN 1Burin). In this family the syndrome is related to a novel MEN 1 gene mutation (deletion of A) at nucleotide 1021 of codon 304 resulting in frame shift and downstream protein truncation at codon 320. Compared to mainstream MEN 1, MEN 1Burin is characterized by a high prevalence of prolactin-secreting pituitary adenomas, late-onset of hyperparathyroidism and rare pancreatic involvement. The family described represents the fifth in the literature with the MEN 1Burin phenotype; 2 out of the other 4 were related to R460X, Y312X respectively and no mutation within the coding sequence of MEN 1 was found in the other 2. Thus, similar to the classic syndrome, MEN 1Burin phenotype shows poor correlation to MEN 1 genotype.

Key-words

MEN 1 Burin variant menin deletion mutation frameshift 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Farid N.R., Buehler S., Russell N.A., Maroun F.B., Allerdice P., Smith H.S. Prolactinomas in familial multiple endocrine neoplasia syndrome type 1. Am. J. Med. 1980, 69: 874–880.PubMedCrossRefGoogle Scholar
  2. 2.
    Bear J.C., Briones-Urbina R., Fahey J.F., Farid N.R. Variant multiple endocrine neoplasia type I (MEN IBurin): further studies and non-linkage to HLA. Hum. Hered. 1985, 35: 15–20.PubMedCrossRefGoogle Scholar
  3. 3.
    Green J.S. Development, implementation and evaluation of clinical and genetic programs for hereditary tumor syndromes, Ph.D. thesis. Memorial University of Newfoundland, St John’s, Newfoundland, Canada, 1995.Google Scholar
  4. 4.
    Petty E.M., Green J.S., Marx S.J., Taggart R.T., Farid N., Bale A.E. Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: Evidence for a founder effect in patients from Newfoundland. Am. J. Hum. Genet. 1994, 54: 1060–1066.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Hershon K.S., Kelly W.A., Shaw C.M., Schwartz R., Bierman E.L. Prolactinomas as part of the multiple endocrine neo-plastic syndrome type 1. Am. J. Med. 1983, 74: 713–720.PubMedCrossRefGoogle Scholar
  6. 6.
    Chandrasekharappa S.C., Guru S.C., Manickam P., Olufemi S.E., Collins F.S., Emmert-Buck M.R., Debelenko L.V., Zhuang Z., Lubensky I.A., Liotta, L.A., Crabtree J.S., Wang Y., Roe B.A., Weisemann J., Boguski M.S., Agarwal S.K., Kester M.B., Kim Y.S., Heppner C., Dong Q., Spiegel A.M., Burns A.L., Marx S.J. Positional cloning of the gene for multiple endocrine neoplasia type 1. Science 1997, 276: 404–407.PubMedCrossRefGoogle Scholar
  7. 7.
    The European Consortium on MEN 1. Identification of the multiple endocrine neoplasia type 1 (MEN 1) gene. Hum. Mol. Genet. 1997, 6: 1177–1183.CrossRefGoogle Scholar
  8. 8.
    Agarwal S.K., Kester M.B., Debelenko L.V., Heppner C., Emmert-Buck M.R., Skarulis M.C., Doppman J.L., Kim Y.S., Lubensky I.A., Zhaung Z., Green J.S., Guru S.C., Manickam P., Olufemi S.E., Liotta L.A., Chandrasekharappa S.C., Collins F.S., Burns A.L., Marx S.J. Germline mutations of the MEN 1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum. Mol. Genet. 1997, 6: 1169–1175.PubMedCrossRefGoogle Scholar
  9. 9.
    Olufemi S.E., Green J.S., Manickam P., Guru S.C., Argawal S.K., Kester M.B., Dong Q., Burns A.L., Speigel A.M., Marx S.J., Collins F.S., Chandra-sekharappa S.C. Common ancestral mutation in the MEN I gene is likely responsible for the prolactinoma variant of MEN I (MEN IBurin) in four kindreds from Newfoundland. Hum. Mutat. 1998, 11: 264–269.PubMedCrossRefGoogle Scholar
  10. 10.
    Marx S.J., Agarwal S.K., Kester M.B., Heppner C., Kim Y.S., Skarulis M.C., James L.A., Goldsmith P.K., Saggar S.K., Park S.Y., Spiegel A.M., Burns A.L., Debelenko L.V., Zhuang Z., Lubensky I.A., Liotta L.A., Emmert-Buck M.R., Guru S.C., Manickam P., Crabtree J.S., Erdos M.R., Collins F.S., Chanra-sekharappa S.C. Multiple endocrine neoplasia type I: Clinical and genetic features of the hereditary endocrine neoplasia. Recent Prog. Horm. Res. 1999, 54: 397–439.Google Scholar
  11. 11.
    Darling T.N., Skarulis M.C., Steinberg S.M., Marx S.J., Spiegel A.M., Turner M. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type I. Arch. Dermatol. 1997, 133: 853–857.PubMedCrossRefGoogle Scholar
  12. 12.
    Waterlot C., Porchet N., Bauters C., Decoulx M., Wemeau J.L., Proye C., Degrand P.M., Aubert J.P., Cortet C., Dewailly D. Type 1 multiple endocrine neoplasia (MEN1): contribution of genetic screening and follow-up of a large French kindred. Clin. Endocrinol. (Oxf.) 1999, 51: 101–107.CrossRefGoogle Scholar
  13. 13.
    Guru S.C., Goldsmith P.K., Burns A.L., Marx S.J., Spiegel A.M., Collins F.S., Chandrasekharappa S.C. Menin, the product of the MEN1 gene, is a nuclear protein. Proc. Natl. Acad. Sci. USA 1998, 95: 1630–1634.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Gobl A.E., Berg M., Lopez-Egido J.R., Oberg K., Skogseid B., Westin G. Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism. Biochem. Biophys. Acta 1999, 1447: 51–56.PubMedGoogle Scholar
  15. 15.
    Agarwal S.K., Guru S.C., Heppner C., Erdos M.R., Collins F.S., Park S.Y., Saggar S., Chandrasekharappa S.C., Collins F.S., Spiegel A.M., Marx S.J., Burns A.L. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 1999, 96: 143–152.PubMedCrossRefGoogle Scholar
  16. 16.
    Kim Y.S., Burns A.L., Goldsmith P.K., Heppner C., Park Y.S., Chandrasekharappa S.C., Collins F.S., Spiegel A.M., Marx S.J. Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene 1999, 18: 5936–5942.PubMedCrossRefGoogle Scholar
  17. 17.
    Kaji H., Canaff L., Goltzman D., Hendy G.N. Cell cycle regulation of menin gene expression. Cancer Res. 1999, 59: 5097–5101.PubMedGoogle Scholar
  18. 18.
    Ikeo Y., Sakurai A., Hashizume K. Characterization of the MEN1 gene product, menin, by site-specific polyclonal antibodies. Jpn. J. Cancer Res. 1999, 90: 1088–1095.PubMedCrossRefGoogle Scholar
  19. 19.
    Waulot V., Khodaei S., Frappart L., Buisson N., Baro E., Lenoir G.M., Calender A., Zhang C.X., Weber G. Expression analysis of endogenous menin, the product of the multiple endocrine neoplasia type I gene, in cell lines and human tissues. Int. J. Cancer 2000, 85: 877–881.CrossRefGoogle Scholar
  20. 20.
    Knudson A.G., Strong L.C., Anderson D.E. Heredity and cancer in man. Prog. Med. Genet. 1973, 9: 113–158.PubMedGoogle Scholar
  21. 21.
    Benvenga S., Bartolone L., Facchiano A., Trimarchi F. Homologies of Menin with tumor suppressor gene products and other proteins. J. Endocr. Genet. 2000, 1: 221–230.Google Scholar
  22. 22.
    Williams J.B., Rexer B., Sirripurapu S., John S., Goldstein R., Phillips J.A. III, Haley L.L., Sait S.N., Shows T.B., Smith C.M., Gerhard D.S. The human HNP36 is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia type 1 (MEN I) syndrome. Genomics 1997, 42: 325–330.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2001

Authors and Affiliations

  • C. Kong
    • 1
  • S. Ellard
    • 2
  • C. Johnston
    • 1
  • Nadir R. Farid
    • 1
  1. 1.Department of EndocrinologyHemel Hempstead General HospitalHemel HempsteadUK
  2. 2.Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health SciencesUniversity of Exeter and The Molecular Genetics Laboratory, Royal Devon and Exeter HospitalExeterUK

Personalised recommendations