title: Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.
abstract: The analysis of APC and MYH mutations in adenomatous polyposis coli patients should provide clues about the genetic heterogeneity of the syndrome in human populations. The entire coding region and intron-exon borders of the APC and MYH genes were analyzed in 60 unrelated Italian adenomatous polyposis coli patients. APC analysis revealed 26 point mutations leading to premature termination, one missense variant and one deletion spanning the entire coding region in 32 unrelated patients. Novel truncating point mutations included c.1176_1177insT (p.His393_PhefsX396), c.1354_1355del (p.Val452_SerfsX458), c.2684C>A (p.Ser895X), c.2711_2712del (p.Arg904_LysfsX910), c.2758_2759del (p.Asp920_CysfsX922), c.4192_4193del (p.Ser1398_SerfsX1407), c.4717G>T (p.Glu1573X) and a novel cryptic APC exon 6 splice site. MYH analysis revealed nine different germline variants in nine patients, of whom five were homozygotes or compound heterozygotes. The mutations included 4 novel MYH missense variants (c.692G>A, p.Arg231His; c.778C>T, p.Arg260Trp; c.1121T>C, p.Leu374Pro; and c.1234C>T, p.Arg412Cys) affecting conserved amino acid residues in the ENDO3c or NUDIX domains of the protein and one novel synonymous change (c.672C>T, p.Asn224Asn). Genotype-phenotype correlations were found in carriers of APC mutations but not in carriers of biallelic MYH mutations, except for a negative correlation with low number of polyps. A distinctive characteristic of patients negative for APC and MYH mutations was a significantly (p<0.0001) older age at diagnosis compared to patients with APC mutations. Moreover, the proportion of cases with an attenuated polyposis phenotype was higher (p = 0.0008) among patients negative for APC and MYH mutations than among carriers of APC or biallelic MYH mutations.
authors.affiliation: Department of Oncology and Neurosciences, University G. D'Annunzio, Chieti, Italy.
authors.forename: Gitana
authors.initials: G
authors.lastname: Aceto
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Curia
authors.forename: Serena
authors.initials: S
authors.lastname: Veschi
authors.forename: Laura
authors.initials: L
authors.lastname: De Lellis
authors.forename: Sandra
authors.initials: S
authors.lastname: Mammarella
authors.forename: Teresa
authors.initials: T
authors.lastname: Catalano
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Palka
authors.forename: Rosa
authors.initials: R
authors.lastname: Valanzano
authors.forename: Francesco
authors.initials: F
authors.lastname: Tonelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Casale
authors.forename: Vittoria
authors.initials: V
authors.lastname: Stigliano
authors.forename: Francesco
authors.initials: F
authors.lastname: Cetta
authors.forename: Pasquale
authors.initials: P
authors.lastname: Battista
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cama
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007558:Italy; D009154:Mutation; D010641:Phenotype
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase