Suha M. Hassan

Extended Molecular Spectrum of β- and α-Thalassemia in Oman

Sickle cell disease is known to be very common in the Omani population, although data are limited concerning β-thalassemia (β-thal). We report the molecular background of 87 unrelated patients from the Sultanate of Oman, diagnosed with β-thal major (β-TM), β-thal intermedia (β-TI) or minor. Diagnosis was based on clinical and hematological data and confirmed by molecular analysis. We found 11 different β-thal determinants in our cohort, which consists of subjects from different regions of Oman. Six of these mutations have not been previously reported in the Omani population. The prevalence of α-thal single gene deletions (−α3.7 and −α4.2) in the same cohort was very high (58.3%). These data will contribute to the implementation of a country-wide service for early molecular detection of hemoglobinopathies and for providing genetic counseling following premarital screening.

Molecular spectrum of α-globin gene defects in the Omani population.

Abstract We describe the molecular characterization of α-globin gene defects in a cohort of 634 Omani patients. A total of 21 different α gene mutations were found in 484 subjects. Overall, we identified three different large deletions, three small deletions, 11 point mutations [two on the α2 polyadenylation signal (polyA) (HBA2: c.*94A>G), and nine α chain variants], three αααanti 3.7 triplication, a 21 nucleotide (nt) duplication on the α1 gene and two novel (presumed) polymorphisms on the α 3.7 kb hybrid gene, namely −5 (C>T) and +46 (C>A). Of these defects, 15 have not been previously reported in the Omani population. This large heterogeneity of α-thalassemia (α-thal) observed in the Omani population could be expected in neighboring Arab countries. The high frequency of α-thal, solely or in association with β-globin gene defects, emphasize the necessity of adding α-thal testing to pre marital programs for accurate genetic counseling.

Sickle cell anemia and α-thalassemia: A modulating factor in homozygous HbS/S patients in Oman

We report the general phenotype severity and the hematological presentation in a cohort of 125 sickle cell anemia (SCA) patients with identical homozygous HbS/S genotype and categorized by identical β(S) haplotype, both with and without alpha thalassemia. No clear general phenotype correlation was found when patients were compared regardless of the haplotype but overall, patients with homozygous alpha thalassemia (α-/α-) had the highest Hb, HCT, RBC and the lowest MCV, MCH and MCHC levels. When patients with identical haplotype were compared, the mildest hematological and clinical conditions were observed in patients of the Asian/Asian haplotype, also known as Arab-Indian haplotype, and carriers of α-thalassemia, suggesting an additional ameliorating effect of alpha thalassemia. In conclusion, our results show that alpha thalassemia improves the hematological conditions but amelioration of the general disease severity is only noticed when compared in cohorts of the same haplotype.

Known and New δ-Globin Gene Mutations and Other Factors Influencing Hb A2 Measurement in the Omani Population

Abstract Although δ-thalassemia (δ-thal) is not categorized as a severe disease, it is essential to know the molecular spectrum of the δ gene mutations frequently occurring in specific areas, particularly if these areas are characterized by a high rate of β-thalassemia (β-thal) such as Oman. This is because coinherited δ-globin gene defects can interfere with the basic diagnosis of a β-thal carrier when this is based upon the measurement of the Hb A2 only. Because of that, we have investigated 33 patients with low Hb A2 levels, collected from different hospitals in Oman. Some cases had a second Hb A2 fraction, while others had only significantly lower Hb A2 levels. Among these patients, 20 did carry a δ-globin gene mutation, the rest were carriers of α thalassemia (α-thal) defects or could be iron depleted or both. In total, eight different known mutations and two novel δ variants were found. The characterization of the δ-globin gene mutation spectrum will improve carrier diagnostics and genetic counseling in the Omani population screened for β-thal.

Broader Spectrum of β-Thalassemia Mutations in Oman: Regional Distribution and Comparison with Neighboring Countries

Abstract The objective of this study was to expand and study the molecular spectrum of β-thalassemia (β-thal) mutations in Oman by examining cases from seven different regions and comparing the prevalence with neighboring countries. A total of 446 cases of β hemoglobinopathies was obtained and analyzed to determine the frequency and distribution of the different β alleles. The molecular spectrum of β-thal in Oman revealed the presence of 32 mutations from different origins and 11 alleles are reported for the first time in the Omani population. The wide heterogeneous spectrum of β-thal mutations found can be associated with the history of trade and migration as well as the past domination from other countries. The presented data will facilitate the development of a comprehensive prevention strategy in Oman.

Hb Lansing (HBA2: c.264C > G) and a New β Promoter Transversion [−52 (G > T)]: An Attempt to Define the Phenotype of Two Mutations Found in the Omani Population

Abstract We report two examples showing how problematic it can be to define the phenotype of new or rare globin genes mutations. We describe two mutations observed for the first time in the Omani population: the first was found in the consanguineous parents of a deceased newborn with hepatomegaly, cardiomegaly and severe hemolytic anemia, putatively homozygous for the rare Hb Lansing (HBA2: c.264C > G) variant. The second is a novel β-globin gene promoter mutation [−52 (G > T)] observed in four independent patients. Two with borderline/elevated Hb A2, α-thalassemia (α-thal) and hypochromic red cell indices, and two heterozygotes for Hb S (HBB: c.20A > T), α-thal and with Hb A/Hb S ratios possibly indicating a very mild β+-thalassemia (β+-thal) mutation.

Repository of mutations from Oman: The entry point to a national mutation database

The Sultanate of Oman is a rapidly developing Muslim country with well-organized government-funded health care services, and expanding medical genetic facilities. The preservation of tribal structures within the Omani population coupled with geographical isolation has produced unique patterns of rare mutations. In order to provide diagnosticians and researchers with access to an up-to-date resource that will assist them in their daily practice we collated and analyzed all of the Mendelian disease-associated mutations identified in the Omani population. By the 1 st of August 2015, the dataset contained 300 mutations detected in over 150 different genes. More than half of the data collected reflect novel genetic variations that were first described in the Omani population, and most disorders with known mutations are inherited in an autosomal recessive fashion. A number of novel Mendelian disease genes have been discovered in Omani nationals, and the corresponding mutations are included here. The current study provides a comprehensive resource of the mutations in the Omani population published in scientific literature or reported through service provision that will be useful for genetic care in Oman and will be a starting point for variation databases as next-generation sequencing technologies are introduced into genetic medicine in Oman.