title: Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene.
abstract: Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene, which is located within this region, was considered to be a good candidate for the MEN 1 gene. In this study, the structure and expression of the PLC beta 3 gene in MEN 1 patients were investigated in more detail, to determine its potential role in MEN 1 tumorigenesis. Southern blot analysis, using blood and tumor DNA from affected persons from seven different MEN 1 families, did not reveal structural abnormalities in the PLC beta 3 gene. To detect possible point mutations, or other small structural aberrations, direct sequencing of PLC beta 3 cDNAs from two affected persons from two different MEN 1 families was performed, but no MEN 1-specific abnormalities were revealed. Several common nucleotide sequence polymorphisms were detected in these cDNAs, proving that both alleles of the PLC beta 3 gene were expressed and analyzed. In conclusion, these results exclude the PLC beta 3 gene as a candidate gene for MEN 1.
authors.affiliation: Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: de Wit
authors.forename: R M
authors.initials: RM
authors.lastname: Landsvater
authors.forename: R J
authors.initials: RJ
authors.lastname: Sinke
authors.forename: A
authors.initials: A
authors.lastname: Geurts van Kessel
authors.forename: C J
authors.initials: CJ
authors.lastname: Lips
authors.forename: J W
authors.initials: JW
authors.lastname: Höppener
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D004262:DNA Restriction Enzymes; D018076:DNA, Complementary; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000201:enzymology / Q000235:genetics*; D054799:Phospholipase C beta; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values; D015183:Restriction Mapping; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D007527:Isoenzymes; D004262:DNA Restriction Enzymes; D010738:Type C Phospholipases; C518039:PLCB3 protein, human; D054799:Phospholipase C beta