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

• Published in: Human mutation 2000-09, Vol.16 (3), p.269-269
• Main Authors: Jakobovitz-Picard, Orit, Olchovsky, David, Berezin, Meir, Ghodsizade, Azizela, Zahavi, Zvi, Karasik, Avraham, Rechavi, Gideon, Friedman, Eitan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; DNA Mutational Analysis; Female; Genes, Tumor Suppressor - genetics; Germ-Line Mutation - genetics; germline mutations; Haplotypes - genetics; Humans; isolated hyperprolactinoma; Israel; Male; MEN1 gene; Middle Aged; Multiple Endocrine Neoplasia Type 1 - genetics; Neoplasm Proteins - genetics; PCR-sequencing; Pedigree; Proto-Oncogene Proteins; Sequence Deletion - genetics
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/1098-1004(200009)16:3<269::AID-HUMU11>3.0.CO;2-2

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.