EXCLUSION OF ZFM1 AS A CANDIDATE GENE FOR MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 (MEN1)

The multiple endocrine neoplasia type 1 (MEN1) locus has been previous ly localised to 11q13 by combined tumour deletion mapping and linkage studies and a 3.8-cM region flanked by PYGM and D11S97 has been define d. The zinc finger in the MEN1 locus (ZFM1) gene, which has also been mapped to this region, represents a candidate gene for MEN1. The ZFM1 gene, which consists of 14 exons, encodes a 623-amino acid protein and exons 2, 8 and 12 encode the putative nuclear localisation signal, a zinc finger motif, and a proline-rich region, respectively. We have in vestigated these potentially functional regions for germ-line mutation s by single-stranded conformational polymorphism (SSCP) analysis in 64 unrelated MEN1 patients. In addition, we performed DNA sequence analy sis of all the 14 exons and 13 of the 26 exon-intron boundaries in fou r unrelated MEN1 patients. A 6-bp deletion that resulted in the loss o f two proline residues at codons 479 and 480 in exon 12 was found in o ne MEN1 patient. However, this did not co-segregate with MEN1 in the f amily and represented a rare polymorphism. Analysis by SSCP, DNA seque ncing, northern blotting, Southern blotting and pulsed field gel elect rophoresis revealed no additional genetic abnormalities of ZFM1 in the other MEN1 patients. Thus, our results indicate that ZFM1 is excluded as a candidate gene for MEN1.