Hereditary Forms of Colorectal Adenomatous Polyposis
Kohoutová M., Štekrová J., Šulová M., Zídková K., 1Kleibl Z., Vandrovcová J., Kebrdlová V., Kotlas J., 2Jirásek V.
Ústav biologie a lékařské genetiky 1. LF UK a VFN, Praha 1Ústav biochemie a experimentální onkologie 1. LF UK, Praha 2IV. interní klinika 1. LF UK a VFN, Praha
Background. Hereditary colorectal adenomatous polyposis syndromes are a predisposition to colorectal carcinoma
development. The familial adenomatous polyposis is the most common analyzed syndrome that results from germline
mutations in the APC gene. In addition to, the autosomal recessive form of polyposis has been recently reported.
This disease is caused by germ-line mutations in the base excision repair MYH gene. The goal of this study is the
identification of genetic causes of the colorectal polyposis, the determination of the frequency and type of the APC
and MYH germ-line mutations in the set of families with colorectal polyposis in Czech population.
Methods and Results. The set of 103 probands with FAP was screened for germ-line APC mutations using the
Protein Truncation Test and Denaturing Gradient Gel Electrophoresis. The MYH mutational screening was performed
on 60 unrelated patients without detected APC mutations using the Denaturing High Performance Liquid
Chromatography. Automated sequencing was carried out to identify found mutations. Totally, the 51 germ-line APC
mutations (69,9 %) are reported in the set of 72 probands including 31 novel mutations unique for Czech population.
Molecular genetic analysis of the MYH gene revealed 15 DNA variations (25 %) including two patients identified as
p.Y165C/p.G382D compound heterozygotes (3,3 %) and 13 polymorphisms or intronic changes (21,7 %). The novel
variants were detected in the 5 patients.
Conclusion. Present study reflects the extremely heterogenous spectrum of the APC mutations in Czech population
and confirms the previously reported data. However, the changes found in the MYH gene still need more extensive
studies. Our results are important for genetic counselling and further clinical management among at-risk family
members. It also enables distinction among different types of the colorectal polyposis.
familial adenomatous polyposis, APC gene, MYH gene, mutational analysis.