title: MUTYH-associated colon disease: adenomatous polyposis is only one of the possible phenotypes. A family report and literature review.
abstract: OBJECTIVE
  The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome.
  
  
  METHODS
  A family with a history of right-sided colon cancer and multiple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MUTYH and the role of prophylactic surgery.
  
  
  RESULTS
  Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, developed four hyperplastic lesions, while the heterozygote brother had a large flat serrated adenoma of the right colon removed at the age of 50.
  
  
  CONCLUSIONS
  Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrated adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP.
authors.affiliation: Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari, Italy. gizorcolo@hotmail.com
authors.forename: Luigi
authors.initials: L
authors.lastname: Zorcolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fantola
authors.forename: Luisa
authors.initials: L
authors.lastname: Balestrino
authors.forename: Angelo
authors.initials: A
authors.lastname: Restivo
authors.forename: Caterina
authors.initials: C
authors.lastname: Vivanet
authors.forename: Francesca
authors.initials: F
authors.lastname: Spina
authors.forename: Francesco
authors.initials: F
authors.lastname: Cabras
authors.forename: Rossano
authors.initials: R
authors.lastname: Ambu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Casula
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D000328:Adult; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D003113:Colonoscopy; D045647:DNA Glycosylases / Q000235:genetics*; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D006965:Hyperplasia; D008221:Lymphoid Tissue; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011322:Primary Prevention; D013577:Syndrome
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase