Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas.
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.
Isidro
Glória
G
Instituto Nacional de Saúde Dr Ricardo Jorge, Centro de Genética Humana, Lisboa, Portugal. gloria.isidro@insa.min-saude.pt
Laranjeira
Francisco
F
Pires
Ana
A
Leite
Júlio
J
Regateiro
Fernando
F
Castro e Sousa
F
F
Soares
José
J
Castro
Clara
C
Giria
João
J
Brito
Maria J
MJ
Medeira
Ana
A
Teixeira
Ricardo
R
Morna
Henrique
H
Gaspar
Isabel
I
Marinho
Carla
C
Jorge
Rosa
R
Brehm
António
A
Ramos
J Silva
JS
Boavida
Maria Guida
MG
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
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase