Mutations Associated with Beta-Thalassemia intermedia in Kuwait

Objective: To identify the β-globin gene mutations associated with β-thalassemia (β-thal) intermedia in Kuwait. Subjects and Methods: Eighteen patients from 13 unrelated families, mean age 12.7 ± 8.1 years, range 4–31 years, were involved in the study. They did not require regular blood transfusion. Complete blood count and cation exchange high-performance liquid chromatography hemoglobin quantitation were carried out using standard techniques. β-Thal mutations were identified with a combination of PCR amplification, allele- specific oligonucleotide hybridization or direct DNA sequencing. The patients were also screened for the α2-globin gene (–3.7 kb) deletion. Results: Of the 13 families, 4 were homozygous for the IVS-I-II (G→A) and 4 for the IVS-I-6 (T→C) mutations, while 1 each was a compound heterozygote for the following mutation combinations: CD 8 (–AA) and –101 (C→T); IVS-I-6 (T→C) and CD 19 (A→G); IVS-II-1 (G→A) and –28 (A→C); IVS-I-110 (G→A) and δβ0 deletion. Therefore, homozygosity for two typically mild mutations (IVS-II-1 and IVS-I-6) accounted for 61% of the genotypes in our patients. Conclusion: Our results indicate that screening should commence with these two common alleles in Kuwaiti patients presenting with β-thal syndrome. Early identification of intermedia patients will avoid the complications following an unnecessary hypertransfusion program.