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Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia
Author(s) -
JakobovitzPicard Orit,
Olchovsky David,
Berezin Meir,
Ghodsizade Azizela,
Zahavi Zvi,
Karasik Avraham,
Rechavi Gideon,
Friedman Eitan
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200009)16:3<269::aid-humu11>3.0.co;2-2
Subject(s) - men1 , multiple endocrine neoplasia , biology , genetics , exon , germline mutation , intron , mutation , gene , germline , haplotype , microbiology and biotechnology , genotype
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.