Last update: 22/05/2006

Background to disease

OMIM # 131100

Familial multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant disorder characterised by tumours of the parathyroid, anterior pituitary and gastro - intestinal endocrine tissues and a high occurrence of peptic ulcer disease.

The MEN 1 gene was mapped to 11q13.1 - 13.5 by Larsson et al., (1988), there was no evidence for genetic heterogeneity. The target region was narrowed to 12cM (Nakamura et al.,1989) but it wasn’t until 1997 (Chandrasekharappa et al.) that the MEN1 gene was identified and cloned. Their approach was to identify 33 candidate genes in the region, these were reduced to 8 transcripts by analysis of LOH in MEN1 tumours (LOH at 11q is common in MEN 1 tumours). 20 of 26 human ESTs used to identify the 8 transcripts constituted a 1.9kb cDNA contig and had previously been placed on the transcript map between D11S913 and D11S1314. Northern blotting identified a full length 2.8kb transcript expressed in all tissues tested. Mutation analysis by dideoxy fingerprinting of affected individuals confirmed this transcript to be the product of the MEN 1 gene since mutations were found in14/15 unrelated affected individuals.

The MEN 1 gene contains 10 exons spanning 9kb genomic DNA. It encodes a 610 amino acid protein - menin -that shows no homology to any previously identified proteins. Mutations identified were spread across the entire length of the gene with no prevalence of missense or nonsense mutations. Most mutations are predicted to cause loss of protein function, supporting the role of menin as a tumour suppressor (in contrast to Ret oncogene mutations in MEN 2). Tumorigenesis therefore occurs as a result of the deletion or mutation of the cell’s wild type copy of the gene.

Locus

11q13.1

Laboratory analysis

Contact scientist: Ruth Charlton

	Test	Target reporting time (working days)
1.	Predictive testing for familial mutation	10
2.	Sequencing of entire coding sequence	40