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Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis
Author(s) -
Nielsen M,
Hes FJ,
Nagengast FM,
Weiss MM,
MathusVliegen EM,
Morreau H,
Breuning MH,
Wijnen JT,
Tops CMJ,
Vasen HFA
Publication year - 2007
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2007.00766.x
Subject(s) - mutyh , familial adenomatous polyposis , germline , adenomatous polyposis coli , germline mutation , medicine , proband , colorectal cancer , colonoscopy , cancer , genetics , mutation , oncology , cancer research , gene , biology
A small fraction of families with familial adenomatous polyposis (FAP) display an attenuated form of FAP (AFAP). We aimed to assess the presence of germline mutations in the MUTYH and adenomatous polyposis coli ( APC ) genes in AFAP families and to compare the clinical features between the two causative genes. Families with clinical AFAP were selected from the Dutch Polyposis Registry according to the following criteria: (a) at least two patients with 10–99 adenomas diagnosed at age >30 years or (b) one patient with 10–99 adenomas at age >30 years and a first‐degree relative with colorectal cancer (CRC) with a few adenomas, and, applying for both criteria, no family members with more than 100 polyps before the age of 30 years. All probands were screened for germline mutations in the APC and MUTYH genes. Twenty‐five of 315 Dutch families with FAP (8%) met our criteria for AFAP. These families included 146 patients with adenomas and/or CRC. Germline APC mutations were identified in nine families and biallelic MUTYH mutations in another nine families. CRC was identified at a mean age of 54 years (range 24–83 years) in families with APC and at 50 years (range 39–70 years) in families with MUTYH (p = 0.29). APC and biallelic MUTYH mutations are responsible for the majority of AFAP families. Based on our results and those reported in the literature, we recommend colonoscopy once every 2 years in AFAP families, starting surveillance from the late teens in APC mutation carriers and from age 20–25 years in biallelic MUTYH mutation carriers.