Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1

TLDR

MEN1 is an autosomal dominant syndrome causing tumors in parathyroids, enteropancreatic endocrine tissues, and the pituitary, and its gene spans 10 exons encoding a 2.8‑kb transcript. The study aims to identify the MEN1 gene to better understand endocrine tumorigenesis and enable early diagnosis. Sequencing of a minimal 11q13 interval revealed a candidate gene with 12 distinct mutations in 14 probands, encoding a 610‑amino‑acid protein, menin, that shares no similarity with known proteins.

Abstract

Multiple endocrine neoplasia–type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610–amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN1 will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.