Internally shortened menin protein as a consequence of alternative RNA splicing due to a germline deletion in the multiple endocrine neoplasia type 1 gene.

Abstract:

:Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominantly inherited cancer syndrome (OMIM 131100), with tumours in several endocrine glands. In 1997 the responsible tumour suppressor gene was identified and recently it was shown that menin, its encoded protein, represses JunD-activated gene expression. Although many MEN 1 patients have been investigated both clinically and genetically, no genotype-phenotype correlation has been found yet. The vast majority of MEN1 gene mutations involve point mutations. We describe a patient in whom a 26 base pair deletion in the MEN1 gene, comprising part of exon 3 and part of intron 3, causes activation of a cryptic donor splice site at the beginning of exon 3. This germline mutation results in an in frame deletion of 105 nucleotides in MEN1 gene mRNA, i.e. an internal deletion of 35 amino acids in the menin protein. Since the deleted region of menin has been implicated in binding to JunD, this may explain the tumourigenic effect of this mutation. The knowledge of this MEN1 gene germline defect, may be used for presymptomatic identification of MEN 1 disease gene-carriers among family-members of this proband. This enables early detection of tumour development, timely treatment and genetic counseling.

journal_name

Int J Mol Med

authors

Roijers JF,Apel T,Neumann HP,Arnim UV,Lips CJ,Hoppener JW

doi

10.3892/ijmm.5.6.611

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

611-4

issue

6

eissn

1107-3756

issn

1791-244X

journal_volume

5

pub_type

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