Format

Send to

Choose Destination
Sci Rep. 2017 Dec 1;7(1):16697. doi: 10.1038/s41598-017-16988-w.

Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece.

Author information

1
Laboratory of Environmental Mutagenesis and Carcinogenesis, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
2
Molecular Diagnostics Laboratory, INRaSTES, National Centre for Scientific Research "Demokritos", Athens, Greece.
3
University Hospital and Palacky University Olomouc, Olomouc, Czech Republic.
4
First Department of Pediatrics, Aghia Sophia Children's Hospital, University of Athens, Athens, Greece.
5
Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece.
6
Laboratory of Protein Structure and Molecular Modelling, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
7
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.
8
Laboratory of Environmental Mutagenesis and Carcinogenesis, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece. mvoutsin@bio.demokritos.gr.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center