Point mutations in splice sites and promotor (eg, Kozak) sequences → ↓ β-globin synthesis. In contrast to α-globin chain genes, the 2 β-globin chain genes are expressed postnatally only, and therefore there is only postnatal disease. - Prevalent in Mediterranean populations.

β-thalassemia minor (heterozygote): β chain is underproduced. Asymptomatic, ↑ HbA₂ (>3.5%) on electrophoresis.β-thalassemia major (Cooley anemia, homozygote): β chain is absent → Severe microcytic, hypochromic anemia with target cells, teardrop cells, basophilic stippling, and increased anisopoikilocytosis requiring blood transfusion (2° hemochromatosis). - Marrow expansion ("crew cut" on skull x-ray) → skeletal deformities. "Chipmunk" facies.- Extramedullary hematopoiesis → hepatosplenomegaly- ↑ risk of parvovirus B19-induced aplastic crisis- ↑ HbF (α₂γ₂), HbA₂ (α₂δ₂)- Hemolysis causes jaundice and ↑ risk of pigment (bilirubin) gallstones- Disease becomes symptomatic only after 6 months, when fetal hemoglobin declines.- Congestive heart failure (CHF) is most common cause of death.