Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder causing benign tumors in the brain and other vital organs. The genes implicated in disease development are TSC1 and TSC2. Here, we have performed mutational analysis followed by a genotype-phenotype correlation study based on the clinical characteristics of the affected individuals. Twenty unrelated probands or families from Greece have been analyzed, of whom 13 had definite TSC, whereas another 7 had a possible TSC diagnosis. Using direct sequencing, we have identified pathogenic mutations in 13 patients/families (6 in TSC1 and 7 in TSC2), 5 of which were novel. The mutation identification rate for patients with definite TSC was 85%, but only 29% for the ones with a possible TSC diagnosis. Multiplex ligation-dependent probe amplification (MLPA) did not reveal any genomic rearrangements in TSC1 and TSC2 in the samples with no mutations identified. In general, TSC2 disease was more severe than TSC1, with more subependymal giant cell astrocytomas and angiomyolipomas, higher incidence of pharmacoresistant epileptic seizures, and more severe neuropsychiatric disorders. To our knowledge, this is the first comprehensive TSC1 and TSC2 mutational analysis carried out in TSC patients in Greece.

1st Department of Pediatrics Aghia Sophia Children's Hospital University of Athens Athens Greece

Division of Nephrology Department of Pediatrics College of Medicine University of Tennessee Health Science Center; Tuberous Sclerosis Complex Center of Excellence Le Bonheur Children's Hospital; and Children's Foundation Research Institute Memphis TN 38103 Tennessee USA

Laboratory of Environmental Mutagenesis and Carcinogenesis Institute of Biosciences and Applications National Centre for Scientific Research Demokritos Athens Greece

Laboratory of Protein Structure and Molecular Modelling Institute of Biosciences and Applications National Centre for Scientific Research Demokritos Athens Greece

Molecular Diagnostics Laboratory INRaSTES National Centre for Scientific Research Demokritos Athens Greece

Section of Cell Biology and Biophysics Department of Biology National and Kapodistrian University of Athens Panepistimiopolis Zografou Athens Greece

University Hospital and Palacky University Olomouc Olomouc Czech Republic

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