Journal Article

Identification of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

Irma Lemmens, Wim J. M. Van de Ven, Koen Kas, Chang X. Zhang, Sophie Giraud, Virginie Wautot, Nathalie Buisson, Ko De Witte, Janine Salandre, Gilbert Lenoir, Michel Pugeat, Alain Calender, Fabienne Parente, Danielle Quincey, Patrick Gaudray, Mireille J. De Wit, Cornelis J. M. Lips, Jo W. M. Höppener, Shideh Khodaei, Abby L. Grant, Günther Weber, Soili Kytölä, Bin T. Teh, Filip Farnebo, Catherine Phelan, Nicholas Hayward, Catharina Larsson, Anna A. J. Pannett, Simon A. Forbes, J. H. Duncan Bassett and Rajesh V. Thakker

in Human Molecular Genetics

Volume 6, issue 7, pages 1177-1183
Published in print July 1997 | ISSN: 0964-6906
Published online July 1997 | e-ISSN: 1460-2083 | DOI:
Identification of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centromerically by PYGM and telomerically by D11S1783 defined by combined meiotic and tumour deletion mapping studies. Two candidate genes, ZFM1 and PPP2R5B, from this region have been previously excluded, and in order to identify additional candidate genes we used a BAC to isolate cDNAs from a bovine parathyroid cDNA library by direct selection.

One of the novel genes that we identified, SCG2, proved to be identical to the recently published MEN1 gene, which is likely to be a tumour suppressor gene. The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus. Mutational analysis of SCG2 in 10 unrelated MEN1 families identified one polymorphism and nine different heterozygous mutations (one missense, four non-sense, one insertional and three deletional frameshifts) that segregated with the disease, hence providing an independent confirmation for the identification of the MEN1 gene. Figure 1

Schematic representation of the chromosome 11q13 region containing the MEN1 gene. The locations of 19 genes [three of which, VRF, PLCB3 and PYGM, (7,10) are polymorphic], three ESTs (D11S2196E, IB408 and EST103356) and four polymorphic loci (D11S457, D11S427, D11S1783 and D11S449) which were previously established by physical mapping (7) and as part of a sequence ready contig (10) are shown. Family linkage studies (i.e. meiotic mapping) had mapped the MEN1 locus telomeric to VRF and centromeric to D11S1783 (10) and LOH studies of tumours (8,9) indicated a location of MEN1 telomeric to PYGM. The combined results of meiotic mapping and LOH studies indicated that the MEN1 gene was located in the <300 kb region flanked centromerically by PYGM and telomerically by D11S1783. Two candidate genes ZFM1 and PPP2R5B had been excluded as the MEN1 gene by mutational analysis (12,13). The BAC 180J2, which contained PYGM and the more telomeric locus ZFM1, was used to isolate additional cDNAs.

Journal Article.  3786 words.  Illustrated.

Subjects: Genetics and Genomics

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