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

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 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 (I, rs1427407 and rs10189857 for and rs9399137 for ). Eleven different β-thal mutations were found but two of them (: c.118C>T and : c.93-21G>A) accounted for about 70.0% of the β-thal alleles. A relatively high proportion of Hb S (: c.20A>T)/β-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift β-thal mutation (: 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.