Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.

Gitana Aceto, Maria Cristina Curia, Serena Veschi, Laura De Lellis, Sandra Mammarella, Teresa Catalano, Liborio Stuppia, Giandomenico Palka, Rosa Valanzano, Francesco Tonelli, Vincenzo Casale, Vittoria Stigliano, Francesco Cetta, Pasquale Battista, Renato Mariani-Costantini, Alessandro Cama

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)394
Number of pages1
JournalHuman Mutation
Volume26
Issue number4
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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