AN ALGORITHMIC APPROACH TO THE MOLECULAR DIAGNOSIS OF ALPHA THALASSEMIA MUTATIONS IN GABONESE PATIENTS WITH SICKLE CELL TRAIT

Lucrèce M. Délicat-Loembet, PhD*, Jérôme Mezui-me-ndong, Thelesfort Mbang Mboro and Lucas Sicas

ABSTRACT

Background: Hemoglobinopathies represent a large group of quantitative and/or qualitative genetic disorders. The thalassemia syndromes are a diverse group of inherited disorders that can be characterized according to their insufficient synthesis or absent production of one or more of the alpha or β-globin chains. The aim of this study is to determine the presence of alpha-thalassemic mutations in Gabonese sickle cell trait carriers by using molecular biology technologies. Methods: The sample was composed of 450 patients from the 9 administrative provinces of Gabon. The strategy used a succession of procedures including DNA extraction, alpha GeneScan assay, multiplex Gap PCR and an analysis using the GeneMarker software. Results: The results showed deletions of one or more copies of the alpha gene present in both HbAA and HbAS genotypes. Regardless of the genotype considered, the types of alpha gene deletions exist to varying degrees -α/αα the silent carrier was most represented (45% and 52%); -α/-α thalassemia trait or minor (13%; 16%) and --/-α HbH disease (Thalassemia intermedia) at 1% in both phenotypes. The frequency of the α3.7 deletion was 21,42%, as homozygous (− α3.7/− α3.7) 35,71%, 14.28% homozygous αα/αα and 26.59% as heterozygous (− α3.7/αα). The heterozygous α-thal (−α4.2 deletion) was absent. Conclusion: The molecular biology strategy used here allowed us to detect the α3.7 deletion and homozygous form (− α3.7/− α3.7) mutation. Considering the role that thalassemic mutations play on the health of the sickle cell patients, this simple and direct strategy should be used to carry out systematic research within the sickle cell populations of Gabon for a better medical care and a follow-up adapted to each patient.

Keywords: Sickle Cell Trait; ?-Thalassemia, Gap-PCR, GeneScan, Gabon.