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 (αPA1α/αPA1α), often cited as αT-Saudiα/αT-Saudiα, being the most common (53.8%) followed by –α3.7/– –MED I (28.8%). Our cohort also included patients with combinations of αPA1 with other Hb variants: αPA1α/αPA1α with Hb S (HBB: c.20A>T) trait (n = 2), –α3.7/αPA1α (n = 2) and αcodon 19α (HBA2: c.56delG)/αPA1α (n = 1). Nondeletional Hb H disease due to the αPA1 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.
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.