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Heterogeneity at the 5'-end of MEN1 transcripts.

Multiple endocrine neoplasia type 1 is an autosomal dominant familial cancer syndrome. The responsible gene, MEN1, has been isolated and inactivating mutations have been found in the majority of MEN1 families. The underlying genetic defects in the remaining families may be located in yet unidentified regions of the MEN1 gene. Here, we present novel transcripts of MEN1 which vary in the content of their 5'-untranslated region. All transcript variants display upstream exons correctly spliced to MEN1 exon 2. The most commonly seen splice isoform occurred in a region previously published as human intron 1, a region which shows a high conservation between human and rodent MEN1. This splice variant uses an analogous transcription initiation site and identical splice donor/acceptor sites as a major transcript seen in rodent Men1. The newly identified MEN1 isoforms may represent biologically important transcripts and should thus be studied for mutations in the regions enclosed therein.