deletion in α ‐ globin genes increases the concentration of fetal hemoglobin and hemoglobin A 2 in a Saudi Arabian population

The regions of Al-Qatif and Al-Ahssa in the Eastern Province of Saudi Arabia are known for their high prevalence of hemoglobinopathies, including β-thalassemia and sickle cell anemia. Previously, the α-gene deletion has been demonstrated as highly prevalent among populations residing in these two regions. The present study was conducted in order to investigate the implications of the α-globin gene deletion on fetal hemoglobin (HbF) and hemoglobin α2 (HbA2) concentrations in patients with transfusion-dependent β-thalassemia. A total of 166 Saudi patients with transfusion-dependent β-thalassemia and 337 healthy Saudi patients were included in the study. The -α3.7, -α4.2, --FIL, --SEA, --MED and --(20.5) gene deletions were identified using multiplex α-globin deletion polymerase chain reaction. The present study revealed that the -α3.7 gene deletion is the most prevalent (43.5%) in the Saudi populations that were analyzed and is characterized by the deletion of 3,804 base pairs. Numerous genotypes, namely α2/α1α2, α2/α1α12, α2/α2, α2/α1α2, α2/α1, α2/α1α2, α12/α1α12, /α2 and α2/α2 Villiers le Bel were also identified in the investigated population. Furthermore, a gradual increase in the concentration of HbF and HbA2 in patients with β-thalassemia and the number of α-gene deletions was demonstrated; whereas in healthy patients the level of HbA2 was demonstrated to decrease as the number of α-gene deletions increased. Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with β-thalassemia rather than α-globin deletions. Furthermore, the results of the present study also revealed novel α-gene deletion genotypes prevalent in the population studied, namely α1α2/α1α2, α1α2/α1α2, α1α2/α1α2 Handsworth, -α2/α1α2, -α2/-α2 Villiers le Bel and --/α1α2.

[1]  S. Fucharoen,et al.  Fetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches , 2016, Expert review of hematology.

[2]  E. Miri-Moghaddam,et al.  Molecular Characterization of β-Thalassemia Intermedia in Southeast Iran , 2016, Hemoglobin.

[3]  J. Borgio,et al.  In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene , 2016, PloS one.

[4]  M. Steinberg,et al.  Mutations in the β‐globin gene from a Saudi population: an update , 2016, International journal of laboratory hematology.

[5]  J. Borgio.  Molecular nature of alpha-globin genes in the Saudi population , 2015, Saudi medical journal.

[6]  L. Teh,et al.  HbF in HbE/β-thalassemia: A clinical and laboratory correlation , 2015, Hematology.

[7]  M. Steinberg,et al.  Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients. , 2015, Blood cells, molecules & diseases.

[8]  T. Spector,et al.  GENOME-WIDE ASSOCIATION ANALYSES BASED ON WHOLE-GENOME SEQUENCING IN SARDINIA PROVIDE INSIGHTS INTO REGULATION OF HEMOGLOBIN LEVELS , 2015, Nature Genetics.

[9]  C. Farra,et al.  Incidence of Alpha-Globin Gene Defect in the Lebanese Population: A Pilot Study , 2015, BioMed research international.

[10]  C. Farra,et al.  Alpha thalassemia allelic frequency in Lebanon , 2015, Pediatric blood & cancer.

[11]  M. Steinberg,et al.  A novel HBA2 gene conversion in cis or trans: "α12 allele" in a Saudi population. , 2014, Blood cells, molecules & diseases.

[12]  E. Bakker,et al.  Sickle cell anemia and α-thalassemia: a modulating factor in homozygous HbS/S patients in Oman. , 2014, European journal of medical genetics.

[13]  H. Tamary,et al.  Characterization of Two Unique α-Globin Gene Cluster Deletions Causing α-Thalassemia in Israeli Arabs , 2014, Hemoglobin.

[14]  Paula J. Griffin,et al.  Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab‐Indian haplotype is not benign , 2014, British journal of haematology.

[15]  R. Ghassemifar,et al.  Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: laboratory diagnosis and clinical importance , 2013, Pathology.

[16]  J. Borgio,et al.  Spectrum of α-Thalassemia Mutations in Transfusion-Dependent β-Thalassemia Patients from the Eastern Province of Saudi Arabia , 2013, Hemoglobin.

[17]  H. Najmabadi,et al.  The Spectrum of α-Thalassemia Mutations in the Kurdish Population of Northeastern Iraq , 2013, Hemoglobin.

[18]  N. Al-Allawi,et al.  Epidemiological profile of common haemoglobinopathies in Arab countries , 2012, Journal of Community Genetics.

[19]  P. Moi,et al.  KLF1 gene mutations cause borderline HbA(2). , 2011, Blood.

[20]  E. Baysal.  α-Thalassemia Syndromes in the United Arab Emirates , 2011, Hemoglobin.

[21]  S. Jaouni.  Prevalence of thalassemia disorders and hemoglobinopathies in Jeddah, western Saudi Arabia , 2010 .

[22]  C. Peng.  Poor Potential of Proliferation and Differentiation in Bone Marrow Mesenchymal Stem Cells Derived From Children with Severe Aplastic Anemia. , 2009 .

[23]  Mohammad Al-Shahrani.  Steps Toward the Prevention of Hemoglobinopathies in the Kingdom of Saudi Arabia , 2009, Hemoglobin.

[24]  A. Maggio,et al.  Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of β-thalassemia , 2008, Haematologica.

[25]  F. Alswaidi,et al.  Premarital screening for thalassemia and sickle cell disease in Saudi Arabia , 2007, Genetics in Medicine.

[26]  Z. Nasserullah,et al.  Regional experience with newborn screening for sickle cell disease, other hemoglobinopathies and G6PD deficiency. , 2003, Annals of Saudi medicine.

[27]  N. Noguera,et al.  Triplication (/alphaalphaalpha anti3.7) or deletion (-alpha3.7/) association in Argentinian beta-thalassemic carriers. , 2003, Annals of hematology.

[28]  K. Kahrizi,et al.  ALPHA-THALASSEMIA:DELETION ANALYSIS IN IRAN , 2001 .

[29]  A. Ghosh,et al.  Ten Years' Experience of Antenatal Mean Corpuscular Volume Screening and Prenatal Diagnosis for Thalassaemias in Hong Kong , 2000, The journal of obstetrics and gynaecology research.

[30]  J. Clegg,et al.  Rapid detection of α‐thalassaemia deletions and α‐globin gene triplication by multiplex polymerase chain reactions , 2000, British journal of haematology.

[31]  F. Galactéros,et al.  alpha-thalassemia in Bantu population from Congo-Brazzaville: its interaction with sickle cell anemia. , 2000, Human heredity.

[32]  B. Al-Awamy.  Thalassemia syndromes in Saudi Arabia. Meta-analysis of local studies. , 2000, Saudi medical journal.

[33]  M. Mokhtar,et al.  Neonatal screening for sickle cell disease, glucose-6-phosphate dehydrogenase deficiency and a-thalassemia in Qatif and Al Hasa. , 1998, Annals of Saudi medicine.

[34]  T. Merghoub,et al.  Spectrum of β‐Thalassemia Mutations in Oman a , 1998 .

[35]  A. Adekile,et al.  Morbidity, beta S haplotype and alpha-globin gene patterns among sickle cell anemia patients in Kuwait. , 1996, Acta haematologica.

[36]  M. El-Hazmi.  Alpha-thalassemia in Saudi Arabia: deletion pattern. , 1987, Human genetics.