Genetic Background of p-Thalassemia in Northeast Algeria with Assessment of the Thalassemia Severity Score and Description of a new (3°-Thalassemia Frameshift Mutation {HBB: c.374dup; p.Pro126Thrfs*15)

摘要

beta-Thalassemia (P-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 p-thal mutations in patients with major hemoglobinopathies [p-thal major (p-TM) and sickle cell disease] in three provinces of northeast Algeria. Our second objective was to assess if the clinical management of p-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 p-thal. Sanger HBB gene sequencing was performed on 59 patients with sickle cell disease and 60 with p-TM. For the latter patients, the genetic modifiers of the TSS were genotyped: ot-thalassemia (a-thal) deletions and four Hb F-inducing polymorphisms (Xmnl, rs1427407 and rs10189857 for BCL11A and rs9399137 for HMIP). Eleven different p-thal mutations were found but two of them [HBB: C.118OT and HBB: c.93-21G>A) accounted for about 70.0% of the p-thal alleles. A relatively high proportion of Hb S [HBB: c.20A>T)/p-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift p°-thal mutation [HBB: c.374dup; p.Pro126Thrfs*15) was identified. No difference was found in the three provinces. Of the 60 p-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.