The relationship of the genetic heterogeneity of sickle cell gene to clinical manifestations.

In Saudi Arabia two major forms of sickle cell anaemia (SCA) have been identified, a benign SCA is reported mainly in the Eastern province and a severe form is reported in other parts of the country. Multiple factors including associated alpha-thalassaemia, elevated Hb F and glucose-6-phosphate dehydrogenase (G-6PD) deficiency have often been reported as modifying the clinical presentation of the disease. However, these factors do not completely explain the amelioration in the clinical manifestations in SCA. More recently interest has been directed toward the investigations of the regions surrounding the beta-globin genes. Using restriction endonucleases extensive polymorphism has been identified and different haplotypes have been encountered. We initiated studies in the different regions of Saudi Arabia. Our studies on the Saudi population from different regions of the country using Hinc II and Hind III showed that the beta-globin gene haplotype ++-++ is associated with a mild sickle cell anaemia, while ----+ is associated with the severe form of the disease. Xmn I polymorphic site 5' to the G gamma gene and 7.6 kb Hpa I fragments 3' to the beta-globin gene are also associated mainly with the mild disease. This paper presents and compares the two major forms of SCA in Saudi population and relates it to the genetic heterogeneity.