title: Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley-Ruvalcaba syndrome.
abstract: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare hamartomatous polyposis condition with features of macrocephaly, intestinal juvenile polyposis, developmental delay, lipomas, and pigmentation spots of the male genitalia. An autosomal dominant pattern of inheritance exists in some families, but others appear as sporadic cases. Germ-line mutations in PTEN, a tyrosine phosphatase and putative tumor suppressor gene, have been demonstrated in two families with BRRS, and chromatin loss at the PTEN gene locus on chromosome 10q23 has been demonstrated in two BRRS patients. Germ-line mutations in PTEN have also been described in Cowden disease and in a small number of patients with juvenile polyposis syndrome. In an attempt to assess the nature of PTEN mutations in BRRS, we analyzed three sporadic BRRS patients for chromosome 10q23 deletion or PTEN germ-line mutations. All 3 patients demonstrated no loss of parental alleles at 15 chromosome 10q23 markers that encompassed the region of PTEN. In addition, analysis of mRNA and genomic DNA revealed no nonsense, missense, or insertion/deletion mutations of PTEN. Thus, other mechanisms besides mutation of PTEN must have occurred to cause BRRS in these patients. We speculate that BRRS and juvenile polyposis syndrome may have a heterogeneous etiology to cause their syndromes.
authors.affiliation: Department of Medicine, Cancer Center, University of California, San Diego 92093-0688, USA. jcarethers@ucsd.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Carethers
authors.forename: F B
authors.initials: FB
authors.lastname: Furnari
authors.forename: A F
authors.initials: AF
authors.lastname: Zigman
authors.forename: J E
authors.initials: JE
authors.lastname: Lavine
authors.forename: M C
authors.initials: MC
authors.lastname: Jones
authors.forename: G E
authors.initials: GE
authors.lastname: Graham
authors.forename: A S
authors.initials: AS
authors.lastname: Teebi
authors.forename: H J
authors.initials: HJ
authors.lastname: Huang
authors.forename: H T
authors.initials: HT
authors.lastname: Ha
authors.forename: D P
authors.initials: DP
authors.lastname: Chauhan
authors.forename: C L
authors.initials: CL
authors.lastname: Chang
authors.forename: W K
authors.initials: WK
authors.lastname: Cavenee
authors.forename: C R
authors.initials: CR
authors.lastname: Boland
mesh_terms: D004247:DNA / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics*; D008297:Male; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D010859:Pigmentation Disorders / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013577:Syndrome; D025521:Tumor Suppressor Proteins
chemical_list: D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human