Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a de crease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treat ment and prevent cardiov ascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is on e of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the futur e and enable even more accessible and accurate genetic diagnostics., M. Vrablík, M. Vaclová, L. Tichý, V. Soška, V. Bláha, L. Fajkusová, R. Češka, M. Šatný, T. Freiberger., and Obsahuje bibliografii
Autosomal dominant hypercholesterolemia (ADH), more known as familial hypercholesterolemia (FH), is a lipid metabolism disorder characterized by an elevation in low-density lipoprotein cholesterol (LDL-C) and increased risk for cardiovascular disea se. In this study, we assessed a spectrum of mutations causing ADH in 3914 unrelated Czech patients with clinical diagnosis of hypercholesterolemia. Samples have been collected within the framework of the MedPed project running in the Czech Republic since 1998. So far we have found 432 patients (11.0 %) with the APOB gene mutation p.(Arg3527Gln) and 864 patients (22.1 %) with the LDLR gene mutation. In 864 probands carrying the LDLR gene mutation, 182 unique allelic variants were detected. We have identified 14 patients homozygous for mutations in the LDLR or APOB genes. We performed function analyses of p.(Leu15Pro) and p.(Gly20Arg) sequence variations., L. Tichý, L. Fajkusová, P. Zapletalová, L. Schwarzová, M. Vrablík, T. Freiberger., and Obsahuje bibliografii
This article describes the evolution of our understanding of familial hypercholesterolemia (FH) in the Central, Eastern, and Southern Europe (CESE) region, and the dissemination of this understanding to other count ries. Using the ScreenPro FH project as an example, we would like to illustrate the progression from national objectives, to regional networking and, finally, to international collaboration via the Familial Hypercholesterolemia Studies Collaboration (FHSC) project under the leadership of the European Atherosclerosis Society (EAS). It is essential to improve our ability to diagnose FH. In this regard, the EAS and its FHSC project must be commended for their educational and organizational activities which, ab ove all, are dedicated to the creation of a global FH patient registry. In the CESE region, FH diagnostics and treatment situation are markedly different than in Western Europe or North America. Since the Czech MedPed project (Make Early Diagnoses to Preve nt Early Deaths in Medical Pedigrees) has been so successful (with results not only comparable to, but, for some parameters, even surpassing the results of many Western countries) we decided to apply the Czech experience to the CESE region. Thus, the ScreenPro FH project was created. The aim of ScreenPro FH is to create a specialist network in the CESE region. The primary objective of the ScreenPro FH project was to dramatically reduce the number of premature deaths due to clinical complications of atherosc lerosis in FH patients. At present, ScreenPro FH comprises 18 member countries with a total population of 500,000,000; which, in terms of the FH population, represents 1-2 million patients., R. Ceska, T. Freiberger, M. Vaclova, T. Aleksicova, L. Votavova, M. Vrablik., and Obsahuje bibliografii
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. Geneti c 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., D. Gabčová, B. Vohnout, D. Staníková, M. Hučkova, M. Kadurová, M. Debreová, M. Kozárová, Ľ. Fábryová, Slovak FH Study Group, J. Staník, I. Klimeš, K. Rašlová, D. Gašperiková., and Obsahuje bibliografii