| Summary: | Neurofibromatosis type 1 (NF1, MIM 162200) is an autosomal dominant disorder affecting about 1 of 3000 live births, involving many cell types and organs, and associated with an increased risk of malignancy, predominantly of the central and peripheral nervous system 1. Tumour development is caused by inactivation of the NF1 tumour suppressor gene and subsequent cell cycle deregulation 2. Mutational analysis of NF1 is a challenge due to the presence of pseudogenes, large size of the gene, lack of mutational hotspots, and occurrence of a very diverse spectrum of mutations. There is no clear-cut genotype-phenotype correlation allowing accurate prediction of severity of the disorder. Only two mutations have been associated with a particular NF1 phenotype 3,4. This PhD thesis is composed of six publications dealing with NF1. Publications 1 and 6 are focused on NF1 mutation analysis in 67 patients from the Czech Republic. Genotypes and spectra of causal mutations are presented together with phenotypes of the patients and comparison of efficiency of various methods. Sporadic or familial cases with known germline mutation were distinguished by mutational analysis of other family members. This led to a hypothesis that the incidence of sporadic cases could had been overestimated in the past because of overlooked...
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