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The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP)

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Abstract
FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of < 100 polyps and a later onset of colorectal cancer (CRC). (A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coil) gene, a tumour suppressor gene that controls beta-catenin turnover in the Wnt pathway. He novo occurrence is reported in 30-40% of the patients. Mutations are detected in 85% of classical FAP families, while only 20%-30% of AFAP cases will exhibit a germline APC mutation. MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations arc inherited in an autosomal recessive way and account for 10%-20% of classical FAP cases without an APC mutation and for 30% of AFAP cases. Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical management. Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary. Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD).
Keywords
genetic counseling, genetics of familial adenomatous polyposis, APC, MutYH, genotype-phenotype correlations, HEREDITARY COLORECTAL-CANCER, MUTATIONS, COLI, MYH, IDENTIFICATION, DIAGNOSIS, LOCUS, CHROMOSOME-5, CARRIERS

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Citation

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Chicago
Claes, Kathleen, Karin Dahan, S Tejpar, Anne De Paepe, Maryse Bonduelle, Marc Abramowicz, Christine Verellen, Denis Franchimont, Eric Van Cutsem, and Alex Kartheuser. 2011. “The Genetics of Familial Adenomatous Polyposis (FAP) and MutYH-associated Polyposis (MAP).” Acta Gastro-enterologica Belgica 74 (3): 421–426.
APA
Claes, Kathleen, Dahan, K., Tejpar, S., De Paepe, A., Bonduelle, M., Abramowicz, M., Verellen, C., et al. (2011). The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). ACTA GASTRO-ENTEROLOGICA BELGICA, 74(3), 421–426.
Vancouver
1.
Claes K, Dahan K, Tejpar S, De Paepe A, Bonduelle M, Abramowicz M, et al. The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). ACTA GASTRO-ENTEROLOGICA BELGICA. 2011;74(3):421–6.
MLA
Claes, Kathleen, Karin Dahan, S Tejpar, et al. “The Genetics of Familial Adenomatous Polyposis (FAP) and MutYH-associated Polyposis (MAP).” ACTA GASTRO-ENTEROLOGICA BELGICA 74.3 (2011): 421–426. Print.
@article{1921421,
  abstract     = {FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70\% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of {\textlangle} 100 polyps and a later onset of colorectal cancer (CRC). 
(A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coil) gene, a tumour suppressor gene that controls beta-catenin turnover in the Wnt pathway. He novo occurrence is reported in 30-40\% of the patients. Mutations are detected in 85\% of classical FAP families, while only 20\%-30\% of AFAP cases will exhibit a germline APC mutation. 
MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations arc inherited in an autosomal recessive way and account for 10\%-20\% of classical FAP cases without an APC mutation and for 30\% of AFAP cases. 
Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical management. 
Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary. 
Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD).},
  author       = {Claes, Kathleen and Dahan, Karin and Tejpar, S and De Paepe, Anne and Bonduelle, Maryse and Abramowicz, Marc and Verellen, Christine and Franchimont, Denis  and Van Cutsem, Eric and Kartheuser, Alex},
  issn         = {0001-5644},
  journal      = {ACTA GASTRO-ENTEROLOGICA BELGICA},
  keyword      = {genetic counseling,genetics of familial adenomatous polyposis,APC,MutYH,genotype-phenotype correlations,HEREDITARY COLORECTAL-CANCER,MUTATIONS,COLI,MYH,IDENTIFICATION,DIAGNOSIS,LOCUS,CHROMOSOME-5,CARRIERS},
  language     = {eng},
  number       = {3},
  pages        = {421--426},
  title        = {The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP)},
  volume       = {74},
  year         = {2011},
}

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