Molecular basis and modern therapeutic possibilities of genetic diseases - Cystic fibrosis as a model
Abstract
In a representative cohort of 248 Czech cystic fibrosis (CF) patients we found the following CFTR gene mutations: ΔF508-71.6%, CFTRdele2,3/21kb/-4.6%, G551D-4.0%, N1303K-3.0%, G542X-2.2%, R347P-0.8%, W1282X-0.6%; 1717-1G->A, R1162X, 3849+ 10kbC->T-0.4% kazda; 2789+5G->A, R334W, R553X, Y122X, 621+ 1 G->T, G85E-02% kazda. Metodou DGGE jsme objevili: 1898+1G->A-2.0%, 2143delT-1.2%; 4374+1G->T, E92X, 2184insA-0.4% each; 2183delAA->G, S1118F, M952L, V1212I, L720F, Y122X, I336K, 185+1C->T, S495L, 3944delGT, S42F-0.2% each (mutations in italics are novel).
Due to the 95.0% detection rate we can provide 100% reliable pre-/postnatal genetic diagnosis of CF. Based on the exact knowledge of the distribution of CFTR gene mutations we can also ascertain the ethnic origin of the Czech population.
Finally, CF is model disease for the implementation of modern pharmacologic and gene-therapeutic approaches in common genetic diseases.