.BETA.0-Thalassemia due to a nonsense mutation at .BETA.90 (GAG.RAR.TAG) in human hemoglobin gene.

We studied a patient with severe anemia and jaundice who exhibited a high hemoglobin A1 (HbA1) level secondary to an increase in HbF despite normal glucose tolerance. The red blood cells showed anisocytosis, poikilocytosis and polychromasia; target cells, Howell-Jolly bodies, Heints bodies and punctate basophilia were observed. No defect or reduction in activity was observed in 19 red cell enzymes. A family history of similar anemia in the patient's daughter and cousins on the mother's side indicated an involvement of genetic factors. Gene cloning and DNA analysis showed that the condition is a new type of β0-thalassemia caused by a nonsense mutation (GAG→TAG) in codon 90 of the β-globin gene.