title: Frequency of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations.
abstract: Tuberous sclerosis (TS) is caused by mutation of the tumor suppressor genes, tuberous sclerosis complex 1 (TSC1) or 2 (TSC2). The aim of the present study was to compare the frequency and types of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations. A meta‑analysis of 380 TS patients was performed. Significant differences were analyzed using the Chi-square test and one-way ANOVA analysis. Results showed a difference in frequency for the four populations analyzed. The frequency of TSC1 mutations was twice as high in the American and British populations. However, there were no significant differences in the types of mutations, with insertions of >1 nucleotide being the least frequent. Additionally, in an analysis of the complexity of nucleotide sequences it was demonstrated that the level of sequence complexity in the Polish population was significant higher compared to the remaining populations. Concerning strand bias, in the case of two types of substitutions, C>G/G>C and C>T/G>A, the ratio of corresponding mutations on the two DNA strands was approximately 3:1 and 2:1. In the present study, an increased frequency of C>G/G>C and C>T/G>A mutations in the coding strand was found in the analyzed populations. However, additional studies and larger patient cohorts are required to verify these results.
authors.affiliation: Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, PL‑02004 Warsaw, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Jóźwiak
authors.forename: Iwona
authors.initials: I
authors.lastname: Sontowska
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D014402:Tuberous Sclerosis / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D006113:United Kingdom; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins