MUTYH gene mutations in Spanish individuals with multiple colorectal adenomas without APC gene mutation.

Abstract

1540 Background: Germ line mutations in the base excision repair MUTYH gene were recently implicated in recessive inheritance of multiple colorectal adenomas without APC mutations. Since the identification of polyposis associated to MUTYH mutations syndrome, different mutations have been described in diverse populations such as Caucasians, Koreans, Portuguese or Pakistanis. In Spanish population is little data about this syndrome. Our aim to describe the type of mutations and estimate its prevalence in Spanish individuals affected with colorectal adenomas with no known APC mutation. Methods: Screening for MUTYH germ line mutations was performed by denaturing liquid chromatography (DHPLC), sequencing and pyrosequencing in 50 Spanish patients with multiple colorectal adenomas with no known APC mutation. The two most prevalent mutations in Caucasian population, Y179C and G396D (previously annotated as Y165C and G382D), were also screened in 80 healthy controls. Results: Biallelic mutations were found in 6 patients (12%): 3 of them (6%) were homozygous for the G396D mutation, 2 (4%) were homozygous for the Y179C mutation, one of whom was carrying the pathogenic mutation Q338X and G396D. One patient (2%) carried a monoallelic Y179C mutation. We identified 4 patients (8%) as monoallelic carriers of unclassified variants at the moment. These variants are: R115G, R426C and P334A. In the control sample, 1 individual (1.25%) was carrier of monoallelic G396D mutation. Conclusions: The estimated prevalence of biallelic MUTYH mutation carriers in patients with colonic polyps is 12%. 50% of these mutations are due to the variant G396D and 43% to the Y179C variant. The monoallelic carrier prevalence in patients with colorectal adenomas is 2%, and the prevalence in healthy population is 1.25%. No significant financial relationships to disclose.