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.