Thalassaemias

The thalassaemias are due to a reduced rate of synthesis of
- or -globin chains, leading to an imbalance in their
production. -thalassaemia is a defect of -globin chain
synthesis. Each normal adult chromosome expresses two copies
of the -globin gene and disease severity is proportional to the
number of -globin genes lost following a mutational event. In
the most severe type, Barts hydrops fetalis, all four copies are
lost, leading to a severe phenotype associated with stillbirth or
early neonatal death. The -globin gene cluster contains a
number of repeat regions that increase the likelihood of
unequal crossover during meiosis. As a result, relatively large
deletions are the commonest type of mutations that give rise to
-thalassamia. In particular, a 3.7 kilobase (kb) deletion is
common in patients from Africa, the Mediterranean, Middle
East and India. A 4.2 kb deletion is common in patients from
southeast Asia and the Pacific Islands. Both 3.7 kb and 4.2 kb
deletions can be detected by PCR analysis; however, since
amplification of the region is often technically challenging,
Southern blotting is still considered a reliable method of
analysis.