Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia

Abstract

Multiple endocrine neoplasia type 1 (MEN‐1) is characterized by hyperfunction and tumor formation of the parathyroids, anterior pituitary and endocrine pancreas. We carried out exon‐specific, PCR‐based DNA sequencing of the coding exons of the MEN1 gene in 8 Israeli MEN1 patients: 4 familial and 4 sporadic. We similarly analyzed Israeli families with a unique phenotype of isolated hyperprolactinemia (HPRL). Four mutations were detected in 4 MEN1 patients: C to T alteration at nucleotide 2608 resulting in R108X, and three intronic insertions/deletions (a 13 basepair (bp) deletion and a 1 bp insertion both in intron 1, and a 2 bp insertion in intron 3) leading to exonic frame shifts as they encompass the splice junctions. An additional patient exhibited a compound mutation: a G to T change at position 7614 resulting in E463X, and insertion/deletion of 9 bp at position 7622‐7630 resulting in EAE466‐468X. Haplotype analysis showed no segregation of phenotype with 11q13 markers in 4 familial HPRL, and no men 1 germline mutations were detected in three representative individuals, from 3 families. Our results confirm that men 1 gene germline mutations occur in the majority of patients with clinically diagnosed MEN1, and that familial HPRL is a genetically distinct disorder. Hum Mutat 16:269, 2000. © 2000 Wiley‐Liss, Inc.

Germline mutations of the MEN1 gene in Korean families with multiple endocrine neoplasia type 1 (MEN1) or MEN1‐related disorders

“…These genetic alterations might be involved in our FIHP family (CUK‐FIHP‐1) without a MEN1 mutation. In contrast to MEN1 or FIHP, previous reports have failed to detect MEN1 germline mutations in familial pituitary diseases (13, 25–29). These results are consistent with our failure to detect MEN1 mutation in the SNU‐FPA‐1 family.…”

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

“…The MEN1 gene is thus proposed to function as a tumorsuppressor gene, as inferred from the frequent allelic loss in MEN-1 -associated tumors (10). Mouse genetic experiments, combined with human genetic data, support the conclusion that MEN1 is a tumor-suppressor gene.…”

Mutant Prolactin Receptor and Familial Hyperprolactinemia

“…2 The occurrence of idiopathic hyperprolactinemia in families has suggested a genetic cause, although investigations for mutations of the multiple endocrine neoplasia type 1 gene (MEN1), which are associated with prolactinomas, have not detected abnormalities. 7 We hypothesized that familial idiopathic hyperprolactinemia may be due to either abnormalities of the prolactin gene (PRL), with the secretion of biologically inactive forms of prolactin, or to prolactin insensitivity caused by a mutation of the prolactin receptor gene (PRLR). Such prolactin insensitivity would be analogous to growth hormone insensitivity and parathyroid hormone resistance resulting in pseudohypoparathyroidism, which are associated with high serum hormone concentrations and have various clinical manifestations.…”