Genetic Background of β-Thalassemia in Northeast Algeria with Assessment of the Thalassemia Severity Score and Description of a new β⁰-Thalassemia Frameshift Mutation (HBB: c.374dup; p.Pro126Thrfs*15)

Abstract

β-Thalassemia (β-thal) is a genetic disorder representing a major health problem in Algeria. Our first objective was to determine the allelic frequencies and molecular spectrum of β-thal mutations in patients with major hemoglobinopathies [β-thal major (β-TM) and sickle cell disease] in three provinces of northeast Algeria. Our second objective was to assess if the clinical management of β-TM patients depended on their region of origin. Our last objective was to assess a population originating from Maghreb, the reliability of the thalassemia severity score (TSS) for patients with homozygous β-thal. Sanger HBB gene sequencing was performed on 59 patients with sickle cell disease and 60 with β-TM. For the latter patients, the genetic modifiers of the TSS were genotyped: α-thalassemia (α-thal) deletions and four Hb F-inducing polymorphisms (XmnI, rs1427407 and rs10189857 for BCL11A and rs9399137 for HMIP). Eleven different β-thal mutations were found but two of them (HBB: c.118C>T and HBB: c.93-21G>A) accounted for about 70.0% of the β-thal alleles. A relatively high proportion of Hb S (HBB: c.20A>T)/β-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift β⁰-thal mutation (HBB: c.374dup; p.Pro126Thrfs*15) was identified. No difference was found in the three provinces. Of the 60 β-TM patients, those with a high or very high TSS were significantly younger at the age of first transfusion, thus assessing the reliability of this scoring system in a Maghrebin cohort. Trends for a lower age of splenectomy and high ferritin levels were also detected for the higher TSS categories.

Keywords:

• Algeria
• epidemiology
• β-thalassemia (β-thal) mutation
• Hb F quantitative trait loci (QTLs)
• thalassemia severity score (TSS)

Disclosure statement

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

Author contributions

W. Abdaoui was the principal investigator who coordinated the research, wrote the first draft of the manuscript and takes primary responsibility; P. Joly supervised the genotyping analyses in France and closely reviewed the manuscript; D. E. Benouareth, A. Djenouni, F. Grifi and M. Benalioua supervised the recruitment in the hematology department in Algeria and/or helped; P. Joly and C. Renoux helped with the genetic data collection and/or HRM methodology; A. Gouri and F. Athamnia helped in the statistical analyses.