A wide heterogeneity of the delta-globin alleles was detected; seven known alleles in trans to the beta-globin gene defects were revealed in 17 out of 18 families, while a new allele in cis to a beta-thalassemia allele was detected in one family.
The phenotype of increased Hb A2 typical of beta-thalassaemia (beta-thal) carriers can be reduced to normal or borderline values because of the co-inheritance of a delta-globin gene (HBD, MIM #142000) mutation, which may lead to misinterpretation of diagnostic results.
Among 7,153 samples studied for beta-thalassemia, 205 samples with lower than expected HbA2 levels were selected for our analysis and 183 samples (2.5%) were positive for delta-globin gene mutations.
In the present study, we quantitate delta-globin mRNA levels in peripheral-blood-enriched reticulocytes and characterize the variation of delta-mRNA levels in 30 beta-thalassemia heterozygotes who individually carry one of the four common Chinese beta-thalassemia alleles [codons 41/42 (-TTCT); codon 17 (A-->T); IVS-II-654 (C-->T); -28 (A-->G)].
During a screening program to identify at risk couples for beta-thalassemia first-trimester prenatal diagnosis, we were able to detect, by polymerase chain reaction (PCR) and direct genomic sequencing of the PCR product, a homozygosis for the G-T substitution at the first nucleotide of codon 27 of the delta-globin gene in a pregnant Sicilian woman.
The synthesis of delta-globin is directed by a gene whose inherent characteristics permit only limited expression, a gene resembling in some respects that of beta +-thalassemia.
This could be a direct result of the gene defect producing beta-thalassemia or be due to differences in the delta-globin gene linked to this beta-thalassemia gene.