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alpha-Thalassaemia in the population of Cyprus
E Baysal1, M Kleanthous, G Bozkurt
1Laboratory of Protein Chemistry, Medical College of Georgia, Augusta 30912-2100.
Insights
This study identified alpha-thalassaemia (alpha-thal) determinants in Cypriot patients with Hb H disease, revealing common and rare alleles. Phenotypic variations in Hb H levels were observed, potentially linked to disease severity.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Alpha-thalassaemia (alpha-thal) is a common inherited blood disorder.
- Hb H disease results from alpha-thal, characterized by reduced hemoglobin production.
- Understanding alpha-thal determinants is crucial for diagnosing and managing Hb H disease.
Purpose of the Study:
- To determine the spectrum of alpha-thal determinants in Cypriot patients with Hb H disease.
- To investigate the frequency of various alpha-thal alleles in Greek and Turkish Cypriot populations.
- To correlate specific alpha-thal genotypes with Hb H disease phenotypes.
Main Methods:
- Genotyping of 78 patients with Hb H disease from Cyprus.
- Analysis of deletional and non-deletional alpha-thal alleles, including specific deletions and point mutations.
- Phenotypic assessment based on hemoglobin levels and red blood cell indices.
Main Results:
- Identified four deletional and three non-deletional alpha-thal alleles, with -alpha(3.7 kb) and --MED-I being most frequent.
- Found a significant prevalence of a non-deletional alpha-thal-2 allele (5 nucleotide deletion in IVS-I) in approximately 8% of chromosomes.
- Observed eight distinct forms of Hb H disease due to various alpha-thal combinations, with notable variations in Hb H levels.
Conclusions:
- The genetic determinants of alpha-thal in Cyprus are diverse, with no significant differences between Greek and Turkish Cypriots.
- Specific alpha-thal genotypes, particularly the alpha 5nt alpha/--MED-I combination, are associated with higher Hb H levels.
- Further research is needed to definitively correlate Hb H levels with disease severity despite observed variations.
Abstract:
We have determined the alpha-thalassaemia (alpha-thal) determinants in 78 patients with Hb H disease from Cyprus; 25 were Turkish Cypriots and 53 were Greek Cypriots. Four deletional and three non-deletional alpha-thal alleles were present; the -alpha(3.7 kb) alpha-thal-2 and the --MED-I alpha-thal-1 were most frequently seen; --MED-II and -(alpha)20.5 deletions occurred at considerably lower frequencies. About 15% of all chromosomes carried a non-deletional alpha-thal-2 allele; of these the 5 nucleotide (nt) deletion at the first intervening sequence (IVS-I) donor splice site was present in approximately 8% of all chromosomes. Two types of polyadenylation signal (poly A) mutations were observed. No striking frequency differences were seen between Greek and Turkish Cypriot patients. Combinations of the various types of alpha-thal resulted in eight different forms of Hb H disease. The phenotypes were comparable except for great variations in the level of Hb H which was highest (average approximately 22%) in the 12 patients with the alpha 5nt alpha/--MED-I combination. One patient with the same form of Hb H disease but with an additional beta-thal (IVS-I-110,G-->A) heterozygosity had a most severe microcytosis and hypochromia with < 1% Hb H. Variations in the level of Hb H might correlate with the severity of the disease, although this was not evident from the haematological data.