First Report on the Coinheritance of α-Thalassemia and a Rare β-Thalassemia Compound Heterozygosity for the IVS-I-I(G>A)/IVS-II-705(T>G) Mutations in a Syrian Family

Abstract

We describe a proband originating from Al-Quneitra Province, Syria. His hematology data was as follows: Hb A 24.7%, Hb F 71.1%, Hb A₂ 4.2%. Molecular analysis, based on DNA sequencing of the β-globin gene mutation, showed for the first time a compound heterozygous IVS-I-1 (G>A) (HBB: c.92+1G>A)/IVS-II-705 (T>G) (HBB: c.316-146T>G) on the β-globin gene. A reverse hybridization technique revealed that the proband was also an α-thalassemia (α-thal) –α^3.7 (rightward) deletion carrier. Haplotypes analysis for the seven polymorphic restriction sites showed that the compound heterozygous mutations, IVS-I-1/IVS-II-705, were linked to two haplotypes: I [+ – – – – + +] and VI [– + + – – – +], respectively. Our results showed, for the first time, the presence of rare β-thalassemia (β-thal) IVS-II-705 (T>G) mutation associated with IVS-I-1 (G>A). Our findings suggest the presence of these mutations resulted from past migrations.

Keywords:

• β-Thalassemia (β-thal)
• β+-thalassemia (β+-thal)
• IVS-II-705 (T>G)
• rare mutations
• Syria

Acknowledgments

We thank Professor I. Othman, Director General of the Atomic Energy Commission of Syria (AECS) and Dr. N. Mirali, head of the Molecular Biology and Biotechnology Department, Human Genetics Division, AECS, Damascus, Syria, for their support.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.