α-Globin Genotypes Associated with Hb H Disease: A Report from Oman and a Review of the Literature from the Eastern Mediterranean Region

Abstract

α-Thalassemia (α-thal) is the most common autosomal recessive hemoglobinopathy. There is a vast diversity and geographical variability in underlying genotypes in Hb H (β4) patients. Herein, we describe the genotypes found in the largest report of Omani Hb H patients. Moreover, we reviewed and summarized the literature published from the Eastern Mediterranean region. A retrospective review of all genetically confirmed Hb H disease patients diagnosed between 2007 and 2017 at Sultan Qaboos University Hospital, Muscat, Oman, was performed. Hematological parameters and clinical presentations were assessed. Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. A total of 52 patients (27 females and 25 males) with a mean age of 20.6 years (range 0.23–80.0) were molecularly confirmed to carry Hb H disease. The patients had a hemoglobin (Hb) level of 9.3 g/dL (range 5.7–13.0) and mean corpuscular volume (MCV) of 58.4 fL (range 48.2–82.1). A total of eight genotype combinations were identified, with α2 polyadenylation signal mutation (polyA1) (AATAAA>AATAAG (α^PA1α/α^PA1α), often cited as α^T-Saudiα/α^T-Saudiα, being the most common (53.8%) followed by –α^3.7/– –^{MED I} (28.8%). Our cohort also included patients with combinations of α^PA1 with other Hb variants: α^PA1α/α^PA1α with Hb S (HBB: c.20A>T) trait (n = 2), –α^3.7/α^PA1α (n = 2) and α^{codon 19}α (HBA2: c.56delG)/α^PA1α (n = 1). Nondeletional Hb H disease due to the α^PA1 mutation is the most common in Omanis. Molecular diagnosis is necessary for accurate confirmation of the diagnosis of α-thal, determination of underlying genotypes, follow-up and counseling.

Keywords:

• Hemoglobinopathy
• molecular genetics
• thalassemia

Acknowledgments

The authors thank all laboratory staff involved in the testing at the Sultan Qaboos University Hospital, Muscat, Oman hematology laboratory.

Author contributions

A.Z. Al-Riyami performed the literature review and drafted the manuscript; both S. Al Zadjali and M. Al Rawahi collected the laboratory data and performed the molecular analysis, S. Al Kindi, A. Al Madhani, Y. Wali and S. Daar were the caregivers of the patients who provided the clinical data for adult and pediatric patients. All authors reviewed and accepted the manuscript before submission.

Disclosure statement

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