Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia.
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.
Jakobovitz-Picard
O
O
The Susanne Levy Gertner Oncogenetics Unit, Endocrine Institute, the Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel.
Olchovsky
D
D
Berezin
M
M
Ghodsizade
A
A
Zahavi
Z
Z
Karasik
A
A
Rechavi
G
G
Friedman
E
E
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins; D017384:Sequence Deletion / Q000235:genetics
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins