title: Molecular Characterization of β-Thalassemia in the Czech and Slovak Populations: Mediterranean, Asian and Unique Mutations.
abstract: β-Thalassemia (β-thal) is considered rare in Central Europe. As in other malaria-free regions, the presence of β-thal in Central Europe reflects historical and recent immigration, and demographic changes that have influenced the genetic variability of the current populations living in this area. This study assesses the frequency and spectrum of mutations on the β-globin gene in Czech and Slovak subjects with clinical symptoms of thalassemia. The results of the initial part of this research were published more than two decades ago; the aim of this study was to update these original reports. During the period from 2002 to 2015, 400 cases from Czech and Slovak hematological centers were analyzed. Twenty-nine β-thal mutations, identified in 356 heterozygotes from 218 unrelated families, involve five unique mutations including a recently described insertion of a transposable L1 element into the β-globin gene. One mutation described here is reported for the first time. Most of the mutations were of Mediterranean origin and accounted for 82.0% of cases. All but one case studied were heterozygous carriers, manifesting β-thal minor, with rare exceptions represented by the rare (β(0)) codons 46/47 (+G) (HBB: c.142_142dupG) mutation associated with an α-globin gene quadruplication and by dominantly inherited β-thal with a more severe phenotype. One double heterozygous β-thal patient was a recent immigrant from Moldavia. The list of δβ-thal alleles (26 carriers, 16 families) contains Hb Lepore and two types of δβ(0)-thal deletions. In the past, genetic drift and migration as well as recent immigrations were responsible for the introduction of Mediterranean alleles, while several mutations described in single families were of local origin.
authors.affiliation: a Department of Hemato-Oncology , Faculty of Medicine and Dentistry, Palacky University and University Hospital , Olomouc , Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Divoka
authors.affiliation: b Department of Biology , Faculty of Medicine and Dentistry, Palacky University , Olomouc , Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Partschova
authors.affiliation: b Department of Biology , Faculty of Medicine and Dentistry, Palacky University , Olomouc , Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kucerova
authors.affiliation: b Department of Biology , Faculty of Medicine and Dentistry, Palacky University , Olomouc , Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Mojzikova
authors.affiliation: d Institute of Hematology and Blood Transfusion , Prague , Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.affiliation: c Department of Pediatrics , Faculty of Medicine and Dentistry, Palacky University and University Hospital , Olomouc , Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospisilova
authors.affiliation: e Department of Hematology and Biochemistry , St. Michael Hospital , Bratislava , Slovak Republic and.
authors.forename: Viera
authors.initials: V
authors.lastname: Fabryova
authors.affiliation: f Department of Pediatrics , Masaryk Hospital , Usti nad Labem , Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Prochazkova
authors.affiliation: a Department of Hemato-Oncology , Faculty of Medicine and Dentistry, Palacky University and University Hospital , Olomouc , Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Indrak
authors.affiliation: a Department of Hemato-Oncology , Faculty of Medicine and Dentistry, Palacky University and University Hospital , Olomouc , Czech Republic.|b Department of Biology , Faculty of Medicine and Dentistry, Palacky University , Olomouc , Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Divoky
mesh_terms: D044466:Asian People / Q000208:ethnology / Q000235:genetics; D018153:Czech Republic / Q000453:epidemiology; D004641:Emigration and Immigration; D005787:Gene Frequency; D040961:Genetic Drift; D006579:Heterozygote; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D010375:Pedigree; D018154:Slovakia / Q000453:epidemiology; D044465:White People / Q000208:ethnology / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000453:epidemiology* / Q000235:genetics
chemical_list: D055544:beta-Globins
keywords: Mediterranean alleles; genetic epidemiology; isolated unique mutations; β-Thalassemia (β-thal)