Molecular analysis of the APC and MYH genes in Czech families affected by FAP or multiple adenomas: 13 novel mutations.

Familial adenomatous polyposis (FAP) is an autosomal dominant predisposition to colorectal cancer and is caused by germline mutations in the adenomatous polyposis coli gene. The most prominent clinical manifestation is the presence of hundreds to thousands of colorectal polyps. A milder phenotype is found in patients affected with AFAP/ multiple adenomas. We screened the entire APC coding region using the combination of DGGE, PTT and direct sequencing and identified causative mutations in 52 of 77 patients. Thirteen of the mutations found were novel. In addition, we also tested 21 APC mutation/negative probands for the two most common mutations in the MYH gene. Four patients showed neither dominant transmission of the disease nor evidence of APC mutations. In one of them the most common biallelic germline mutation in the MYH gene was detected. Correlations between the localization of germline mutations and clinical manifestations of the diseases are discussed.

Vandrovcová J ，Stekrová J ，Kebrdlová V ，Kohoutová M ... -  《-》

Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis.

Nielsen M ，Hes FJ ，Nagengast FM ，Weiss MM ，Mathus-Vliegen EM ，Morreau H ，Breuning MH ，Wijnen JT ，Tops CM ，Vasen HF ... -  《CLINICAL GENETICS》

Mutation analysis of the MYH gene in unrelated Czech APC mutation-negative polyposis patients.

Sulová M ，Zídková K ，Kleibl Z ，Stekrová J ，Kebrdlová V ，Bortlík M ，Lukás M ，Kohoutová M ... -  《EUROPEAN JOURNAL OF CANCER》

[Hereditary forms of colorectal adenomatous polyposis].

Kohoutová M ，Stekrová J ，Sulová M ，Zidková K ，Kleibl Z ，Vandrovcová J ，Kebrdlová V ，Kotlas J ，Jirásek V ... -  《-》

APC germline mutations identified in Czech patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited predisposition to colorectal cancer, which is caused by germline mutations in the adenomatous polyposis coli (APC) gene. The APC mutations have been investigated in 46 Czech unrelated FAP families and 9 suspected FAP families using DGGE analysis and direct DNA sequencing. We found 25 germline APC mutations and identified 11 which were not previously reported. Of the identified mutations, 10 were 1 to 5 bp deletions, four were 1 bp insertions and six were nonsense, all leading to the formation of premature stop codon. In addition, we detected two mutations in the splice-donor region of APC intron 11, one missense and two samesense mutations. Phenotypes of patients with known and novel types of mutations are presented and discussed.

Kohoutová M ，Stekrová J ，Jirásek V ，Kapras J ... -  《-》