The MUTYH gene belongs to the Base Excision Repair (BER) genes. Protein products of these genes are responsible for the mutations repair caused by the reactive oxygen products formed during the aerobe metabolism. Germline mutations of the MUTYH gene are associated with a portion of cases of attenuated familial polyposis (AFAP) with an autosomal recessive type of inheritence. In the intestine of patients with AFAP there are less than 100 adenomatous polyps present. At the same time, it has been demonstrated that also one mutated allele can increase the risk of colorectal carcinoma. Therefore, all polyposis which are connected with mutations in the MUTYH gene have been classified into the MYH-associated polyposis (MAP) group. Other than the intestine matifestations in MAP are seldom frequent. It can be very rarely an endometrial carcinoma. In 2005, the first case was described of the sebaceous tumor as the manifestation of MYH - associated attenuated polyposis caused by the biallelic mutation of the MUTYH gene. Therefore, in the patients with phenotypic manifestations of Muir-Torre syndrome and with unproven mutation in MMR it is necessary to consider the possibility of the MYG gene examination.
The MUTYH gene is localized on the chromosome 1 in the region 1p34.1 and has 16 exons.
We detect mutations in the coding region of the MUTYH gene. Primers for PCR amplification are designed the way that we are able to detect also a possible mutation of the splice site. PCR products are analysed by direct sequencing. Extensive deletions are possible to capture using the MLPA kit, but probes only for exons 2, 3 and 16 are included. Examination is feasible from frozen tissue and blood.
Conventional FAP is in 7 % - 20 % cases caused by the biallelic mutation in the MUTYH gene and AFAP in ~30 % cases.
It is possible to capture ≤ 90 % of mutations by the sequence analysis and ~10 % of extensive deletions/duplications using MLPA.
Sequence analysis of coding sequence and flanking intron regions in combination with MLPA analysis covers 95% of known mutations in MUTYH gene.
Analytical sensitivity and specificity of the sequencing: 99%.
Mutations deep in the introns and regulatory sequences are not detected. Rare polymorphisms in the location of primers annealing may cause a diagnostic error.
In the case of the analysis of somatic mutations by sequencing the mutations will not be detected, if the altered cell line is not represented by at least 20%.
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