title: Novel mutation of the PTEN gene in an Italian Cowden's disease kindred.
abstract: Cowden disease (CD) is an autosomal dominant multiple hamartoma syndrome with an elevated risk of thyroid and breast cancers. The CD susceptibility gene has recently been identified as the PTEN/MMAC1/TEP1 gene localized at 10q23 and coding for a dual specificity protein phosphatase. We report the mutational analysis of the PTEN gene in one Italian CD kindred. By using the single strand conformation polymorphism technique and subsequent direct DNA sequencing of the polymerase chain reaction product, we identified a novel mutation in the exon 5 of the PTEN gene. A heterozygous germline TGT-TAT transition was detected at the nucleotide 407; this causes the amino acid substitution cys136-tyr136 and the generation of a new NSI I restriction site. This mutation was not detected in the unaffected member of the family thereby indicating that it is causally linked to the disease. We ruled out that this mutation is a polymorphic variant because it was not detected in over 100 chromosomes analyzed. Using reverse trancriptase-polymerase chain reaction, we detected the expression of the mutant allele in lymphocytes and pathological tissues from an affected member of the family.
authors.affiliation: Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, via M. Semmola, 80131 Napoli, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Scala
authors.forename: P
authors.initials: P
authors.lastname: Bruni
authors.forename: L
authors.initials: L
authors.lastname: Lo Muzio
authors.forename: M
authors.initials: M
authors.lastname: Mignogna
authors.forename: G
authors.initials: G
authors.lastname: Viglietto
authors.forename: A
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000293:Adolescent; D000483:Alleles; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000235:genetics*; D018095:Germ-Line Mutation; D006042:Goiter / Q000378:metabolism; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D007558:Italy; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011127:Polyps / Q000378:metabolism; D012313:RNA / Q000032:analysis / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D025521:Tumor Suppressor Proteins; D012313:RNA; C048503:ATGCAT-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human