Genetic Background of the Sickle Cell Disease Pediatric Population of Dakar, Senegal, and Characterization of a Novel Frameshift β-Thalassemia Mutation [HBB: c.265_266del; p.Leu89Glufs*2]

Abstract

Sickle cell disease is a genetic disorder with a large variability in the pattern and severity of clinical manifestations. Different genetic modulators have been identified but very few epidemiologic data are available on these modifier genes in Senegal. This study aimed to determine their prevalence in a Senegalese sickle cell disease pediatric population. The following genetic parameters were genotyped in 295 sickle cell disease children of the Dakar pediatric hospital: sickle cell disease genotype [β^S/β^S (HBB: c.20A>T), β^S/β^C (HBB: c.19G>A), β^S/β⁰-thalassemia (β⁰-thal)], XmnI polymorphism, the five most common α-thalassemia (α-thal) deletions and the A(–) and Betica glucose-6-phosphate-dehydrogenase (G6PD) deficient variants. Despite very few β^S/β^C and β^S/β⁰-thal children (1.0% each), a novel frameshift β⁰-thal mutation was characterized: HBB: c.265_266del; p.Leu89Glufs*2. The –α^3.7 (rightward) deletion was the only α-thal deletion identified in this cohort (12.0% allelic frequency). Most of β^S/β^S patients (61.9%) were homozygous for the XmnI polymorphism and assumed to carry a Senegal/Senegal β^S haplotype. The remaining haplotypes were predominantly of the Benin type. While the Betica G6PD variant was quite frequent (13.0%), a low frequency of the A(–) variant was detected (1.0–2.0%). The systematic genotyping of the –α^3.7 deletion and of the G6PD Betica variant in sickle cell disease patients from Senegal could be useful to identify patients at risk for several complications, such as cerebral vasculopathy, where it has been demonstrated that a normal α-globin genotype and G6PD deficiency are predisposing factors. These patients should be eligible for a transcranial Doppler examination that is not routinely offered in Senegal.

Keywords:

• α-Thalassemia (α-thal)
• glucose-6-phosphate dehydrogenase (G6PD) Betica
• novel β-thalassemia (β-thal) mutation
• sickle cell disease
• XmnI polymorphism

Acknowledgments

FGT was the principal investigator who coordinated the research, wrote the paper and takes primary responsibility for it. PJ supervised the genotyping analyses in France and reviewed the paper. PSL, EMD, PMG, RND, PAD and AC supervised the recruitment in Senegal and/or helped. PL and CR helped with the genetic data collection and/or HRM methodology. PC and CM reviewed the paper. IDL and ID are the pediatric hematologists who currently perform the clinical follow-up of the sickle cell disease patients in Dakar. The authors thank Marc Romana (Université des Antilles/Inserm UMR 1134 Biologie Intégrée du Globule Rouge CHU, Hôpital Ricou, Pointe-á-Pitre Guadeloupe, France) for editing the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.