The disease manifests only with homozygosity for Hb S, compound heterozygosity for Hb S and beta-thalassemia, or a different HBB variant that interacts with the Hb S. The most severe variants, such as Hb SS and Hb Sβ0-thalassemia, completely lack normal Hb. The gene discussed is GSTM1; the disease is thalassemia.