ABSTRACT
Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p.Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Genetic etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation.
Subject(s)
Health Surveys , Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/genetics , Receptors, LDL/genetics , Adult , Female , Health Surveys/methods , Humans , Hyperlipoproteinemia Type II/diagnosis , Male , Real-Time Polymerase Chain Reaction/methods , Slovakia/epidemiology , Statistics as Topic/methods , Young AdultABSTRACT
OBJECTIVES: The palatal angle is an important angle of the craniofacial complex. It is significant for the diagnosis of craniofacial disorders mainly for nasopharyngeal soft-tissue patterns.Background The dentists and otorhinolaryngologists use this relationship to establish proper treatment mechanics and evaluate facial profile. The aims of this study were to provide comparative cephalometric analyses of historical and contemporary skulls. MATERIALS AND METHOD: A total of 190 cephalograms of 2 groups of subjects were evaluated. Dolphin Imaging 11.0 - Cephalometric Tracing Analysis was used for the analysis. Unpaired two-tailed t-test assuming equality of variances was used for all variables (at the significance level p = 0.0001). RESULTS: The -modern forensic skulls had larger palatal angle at average value of 8.60 degrees ± 4.35, than that of archeological ones, the average value of which was 6.50 degrees ± 3.92. The difference was found significant. Unpaired two-tailed t-test assuming equality of variances showed that historical and contemporary skulls had statistically significant results. The difference was -2.09 with standard error of 0.60 (95% confidence interval from -3.29 to -0.89). Two-tailed probability attained value of P was less than 0.0001. CONCLUSION: The difference between both groups was found significant. An increase in the palatal angle can be directly connected with anterior rotation of upper jaw(Tab. 2, Fig. 5, Ref. 19).
Subject(s)
Face/anatomy & histology , Fossils/anatomy & histology , Palate/anatomy & histology , Palate/growth & development , Skull Base/anatomy & histology , Skull/growth & development , Adult , Archaeology , Cephalometry/methods , Facial Bones/anatomy & histology , Facial Bones/growth & development , Female , Humans , Male , Mandible/anatomy & histology , Mandible/growth & development , Maxillofacial Development , Skull/anatomy & histology , Skull Base/growth & developmentABSTRACT
DNA interstrand cross-links (ICL) are thought to be one of the most lethal forms of DNA damage. Therefore, they present a colossal challenge for the DNA damage response and repair pathways. In Saccharomyces cerevisiae, ICL repair utilizes factors from all of the three major repair groups: nucleotide excision repair (RAD3 epistasis group), post-replication repair (RAD6 epistasis group) and recombinational repair (RAD52 epistasis group). Moreover, there are additional factors significantly influencing the repair of ICL in this organism. These have been designated PSO1-10 based on the psoralen sensitive phenotype of the corresponding mutants. Phenotype of the pso2 mutant suggests that Pso2 is not involved in incision step of ICL repair, but it rather functions in some downstream event such as processing of DNA ends created during generation of ICL-associated double-strand breaks (DSB). In order to address the question whether function of Pso2 in the repair of ICL-associated DSB could be mediated through protein-protein interactions, we have conducted a comprehensive two-hybrid screen examining a possibility of interaction of Pso2 with Yku70, Yku80, Nej1, Lif1, Dnl4, Rad50, Mre11, Xrs2, Rad51, Rad52, Rad54, Rad55, Rad57, Rad59 and Rdh54. Here we show that Pso2 associates with none of the above DSB repair proteins, suggesting that this protein very likely does not act in the repair of ICL-associated DSB via crosstalk with DSB repair machinery. Instead, its function in this process seems to be rather individual.
