title: Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients.
abstract: BACKGROUND
  Familial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations are point mutations or small insertions/deletions which lead to truncated protein products. Splicing mutations or gross genomic rearrangements are less common inactivating events of the APC gene.
  
  
  METHODS
  In the current study genomic DNA or RNA from ten unrelated FAP suspected patients was examined for germline mutations in the APC gene. Family history and phenotype were used in order to select the patients. Methods used for testing were dHPLC (denaturing High Performance Liquid Chromatography), sequencing, MLPA (Multiplex Ligation - dependent Probe Amplification), Karyotyping, FISH (Fluorescence In Situ Hybridization) and RT-PCR (Reverse Transcription - Polymerase Chain Reaction).
  
  
  RESULTS
  A 250 Kbp deletion in the APC gene starting from intron 5 and extending beyond exon 15 was identified in one patient. A substitution of the +5 conserved nucleotide at the splice donor site of intron 9 in the APC gene was shown to produce frameshift and inefficient exon skipping in a second patient. Four frameshift mutations (1577insT, 1973delAG, 3180delAAAA, 3212delA) and a nonsense mutation (C1690T) were identified in the rest of the patients.
  
  
  CONCLUSIONS
  Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations.
authors.affiliation: Molecular Biology Research Center HYGEIA-Antonis Papayiannist, Athens, Greece. m.mihalat@hygeia.gr
authors.forename: Markos
authors.initials: M
authors.lastname: Mihalatos
authors.forename: Angela
authors.initials: A
authors.lastname: Apessos
authors.forename: Hans
authors.initials: H
authors.lastname: Dauwerse
authors.forename: Voula
authors.initials: V
authors.lastname: Velissariou
authors.forename: Aristidis
authors.initials: A
authors.lastname: Psychias
authors.forename: Alexander
authors.initials: A
authors.lastname: Koliopanos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Petropoulos
authors.forename: John K
authors.initials: JK
authors.lastname: Triantafillidis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Danielidis
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Niki J
authors.initials: NJ
authors.lastname: Agnantis
authors.forename: Georgios
authors.initials: G
authors.lastname: Nasioulas
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D017398:Alternative Splicing; D002851:Chromatography, High Pressure Liquid; D018389:Codon, Nonsense; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D015321:Gene Rearrangement; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D016678:Genome; D018095:Germ-Line Mutation; D006115:Greece; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense