Genetic Mutations

SCD results from several genetic mutations that affect the human b-globin gene. The characteristic defect is a single point mutation, an A®T base transversion (GAG/GAA® GTG/GTA) in the 6th codon of the b-globin gene. This SCD mutation is termed b^S, and results in a single amino acid substitution, b6 Glu®Val. The mutant Hb protein (gene product) is referred to as Hb S[17]. The sickle mutation can occur in the homozygous state, which is classically termed sickle cell anemia or Hb SS (b^S/b^S)[17]. In addition, SCD can occur in (compound) heterozygous states wherein the b^S mutation is present concurrently with other b-globin gene mutations (e.g., b^S/b^C, b^S/b^thal, b^S/b^O-Arab, b^S/b^D-Punjab,  b^S-Antilles)[17-21]. Important pro-sickling mutations include the b^Antilles (b23 Val®Ile) and b^D-Punjab (b121 Glu®Gln) mutations.