Molecular Characterization ofβ-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.

Molecular heterogeneity of β‐thalassemia variants in the Eastern region of Morocco

“…The frequency of this variant was higher in Algeria (10%–14.5%), followed by Morocco (5%–13.3%) and finally, Tunisia (4%) (Abdaoui et al, 2019 ; Agouti, Badens, et al, 2008 ; Chouk et al, 2004 ; Fattoum et al, 2004 ; Labie et al, 1990 ; Lemsaddek et al, 2003 ). Moreover, this variant was also described as the most frequent variant in some European countries such as Czech Republic (27%), Hungary and Middle East countries (Divoka et al, 2016 ; Ghoti et al, 2017 ; Ringelhann et al, 1993 ), and it has been suggested that the variant was originated from Eastern Europe (Makhoul et al, 2005 ). IVS‐II‐1(G > A) in the other side was the most common variant in Iran with a frequency ranging between 25.61% and 40.33% (Jalilian et al, 2017 ; Maryami et al, 2015 ).…”

“…The patient, originated from Guercif, was homozygous, while the parents and the siblings were carriers. The C38/39(‐C) is very rare variant and was only found in Czechoslovakian population and most affected families come from central Moravia (Divoka et al, 2016 ; Indrak et al, 1991 , 1992 ). Previous haplotype analysis studies showed that C38/39(‐C) is linked only to Haplotype II (HindIII Gγ; HinfIβ; HincII β ψ; RsaI β; AvaII β; HindIII Aγ [− + − − − +]) (Kynclová et al, 1998 ) and interestingly in consistent with this data, β 0 C38/39(‐C) was the one and only variant linked to the FWIII in our study, indicating a distinct origin or a recent occurrence.…”

Care for Haemoglobinopathy Patients in Slovakia

“…The methods such as capillary electrophoresis, isoelectric focusation and mass spectrometry dominate the methods worldwide. The final diagnosis is confirmed by genetic tests (20).…”

Hemoglobinopathies

“…Molekulárněgene tická analýza ukázala, že příčinou je mutace CT v pozici 110 G γ [10,11]. Další zajímavé βtalasemické mutace po psali Divoký et al [12,13] a Divoká et al [14]. K dnešnímu dni bylo v ČR popsáno 34 βtalasemických alel v 363 ro dinách u 610 osob.…”