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

Hum Mutat. 2000 Sep;16(3):269. doi: 10.1002/1098-1004(200009)16:3<269::AID-HUMU11>3.0.CO;2-2.

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.

MeSH terms

  • Adolescent
  • Adult
  • DNA Mutational Analysis
  • Female
  • Genes, Tumor Suppressor / genetics
  • Germ-Line Mutation / genetics
  • Haplotypes / genetics
  • Humans
  • Israel
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 / genetics*
  • Neoplasm Proteins / genetics*
  • Pedigree
  • Proto-Oncogene Proteins*
  • Sequence Deletion / genetics

Substances

  • MEN1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins