Molecular Basis of α- Thalassemia in Bahrain

 Jassim N, M.Phil-shaikha Al-Arrayed, MD, PhD-Gerard N,MPhil***Hussain Al-Mukharraq, MD****Abdullah Al-Ajami, MD*****Ducrocoq R, PhD******Nagel RL,MD,PhD******krishnamoorthy R,MD,PhD*** 

Objectives:  this study was designed to delineate the molecular lesions, on DNA level, that lead to α-thalassemia in the population of Bahrain.Methods: Various polymerase chain reaction (PCR)-based methodologies were involved, namely, differential PCR amplification, PCR-restriction fragment length polymorphism (PCR-RFLP), and direct PCR-amplified genomic DNA sequencing.Results:  five α- thalassemia determinates were identified.  These include three deletional type, the rightward 3.7 kilobase (kb) deletion, the leftward 4.2 kb deletion, and the pentanucleotide deletion in 5 splice donor side of intron I in α2-globin gene (GGTGAGG→GG…), and two nondeletional α-thal determinants, the Saudi type polyadenylation (polyA) signal mutation in the α2-globin gene (AATAAA→AATAAG), and the Turkish type polyA signal mutation (AATAAA→AATGAA), also in α2-globin gene.Conclusion:  Three α-thalassemia mutations, the Saudi type polyA signal mutation, the pentanucleotide deletion and the rightwards 3.7 kb deletion, account for 97% of all α-thalassemia determinants in Bahrain.Recommendations: a well-tailored genetic counseling approach, supported by molecular studies, is advised for family members affected with α-thalassemia, and in particular for carries of the polyA signal mutations.  

Bahrain Med Bull 2001;23(1):  3-7.

*                      Molecular Geneticist

**                    Consultant Clinical Geneticist, Genetic Unit

***                  Consultant Paediatric Haematologist & Chief of Medical Stuff

****                Consultant Haematologist, Oncology Unit

                        Salmaniya Medical Complex

                        State of Bahrain

***                  INSERM U 458

******                        Laboratories de  Biochimie Genetique

                        Hospital Robert Debre, Paris, France

*******                      Division of Haematology

Albert Einstein College of Medicine