BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by mental retardation, epilepsy, facial angiofibromas, lesions in the CNS and the occurrence of hamartomata in different tissues. There are two genes responsible (TSC1 and TSC2). The aim of the study is to adopt a diagnosis of the disease on DNA level. METHODS AND RESULTS: 111 DNA samples were collected from 45 families with 54 clinically diagnosed patients. Three families with multiple incidence are linked to chromosome 9. In one case a large deletion was found using TSC2 specific cDNA probes. Most TSC mutations are supposed to be small mutations, identifiable by SSCP method. Using this method we examined all 23 TSC1 exons and 20 out of 41 TSC2 exons. In the TSC1 gene we found 1 nonsense and 2 frameshift mutations and 2 intragenic polymorphisms useful for linkage. In the TSC2 exons was identified so far 6 aberrations, cause of which is being checked by sequencing. CONCLUSIONS: DNA mutation analysis is effective namely in families with multiple incidence. In such families the linkage can be used and there is more TSC1 cases which are easily identifiable. Analysis is not economical for differential diagnosis. Total number of revealed mutations (6.7%) matches last reports. No correlation between phenotype and type of mutation was found.

Ustav lékarské genetiky a fetální medicíny Fakultní nemocnice Olomouc