A 30-year-old man has fatigue from chronic hypochromic microcytic anemia. Hemoglobin electrophoresis reveals decreased Hgb A1 with increased Hgb A2 and F, due to imbalance of alpha and β globin chain synthesis. This results in RBC inclusions that cause membrane damage and accelerate apoptosis. Which of the following mutations is most likely to be present in the β globin gene of this man?
|B.||New stop codon|
Single base insertion, with frameshift
Answer : D Splice site
This is one mechanism for β+ thalassemia. Because introns are usually involved, flanking exons remain, some normal splicing can occur, and some β globin chain synthesis proceeds. The other listed mutations lead to a block in translation, with no functional β globin chain synthesis, typical for β0 thalassemia.