title: Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas.
abstract: Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer. In contrast to the classic dominant condition of familial adenomatous polyposis (FAP) due to germinal mutations in the APC gene, the MYH polyposis is an autosomal recessive disease. The identification of individuals affected by MYH polyposis brings new and important implications for the diagnostic, screening, genetic counseling, follow up and therapeutic options in these patients. In this study, screening for germinal mutations in the MYH gene was performed in 53 Portuguese individuals with multiple colorectal adenomas or classic adenomatous polyposis, in whom no mutation had been identified in the APC gene. The results revealed the presence of biallelic germline MYH mutations in 21 patients. In addition, we here report 3 mutations (c.340T>C [p.Y114H]; c.503G>A [p.R168H]; and c.1186_1187insGG [p.E396fsX437]) which, to our knowledge, have not been previously described.
authors.affiliation: Instituto Nacional de Saúde Dr Ricardo Jorge, Centro de Genética Humana, Lisboa, Portugal. gloria.isidro@insa.min-saude.pt
authors.forename: Glória
authors.initials: G
authors.lastname: Isidro
authors.forename: Francisco
authors.initials: F
authors.lastname: Laranjeira
authors.forename: Ana
authors.initials: A
authors.lastname: Pires
authors.forename: Júlio
authors.initials: J
authors.lastname: Leite
authors.forename: Fernando
authors.initials: F
authors.lastname: Regateiro
authors.forename: F
authors.initials: F
authors.lastname: Castro e Sousa
authors.forename: José
authors.initials: J
authors.lastname: Soares
authors.forename: Clara
authors.initials: C
authors.lastname: Castro
authors.forename: João
authors.initials: J
authors.lastname: Giria
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Brito
authors.forename: Ana
authors.initials: A
authors.lastname: Medeira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Teixeira
authors.forename: Henrique
authors.initials: H
authors.lastname: Morna
authors.forename: Isabel
authors.initials: I
authors.lastname: Gaspar
authors.forename: Carla
authors.initials: C
authors.lastname: Marinho
authors.forename: Rosa
authors.initials: R
authors.lastname: Jorge
authors.forename: António
authors.initials: A
authors.lastname: Brehm
authors.forename: J Silva
authors.initials: JS
authors.lastname: Ramos
authors.forename: Maria Guida
authors.initials: MG
authors.lastname: Boavida
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D003111:Colonic Polyps / Q000453:epidemiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005787:Gene Frequency; D005808:Genes, Recessive; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011174:Portugal / Q000453:epidemiology
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase