The globin genes can present various types of alterations that gives origin to the different forms of thalassaemia.

The most common alterations are the deletions (total absence of the interested gene) or the mutations (small point defects). In both cases the genes loss their function and therefore they do not produce or they produce only in reduced quantity the corresponding globin chains.

The absent or not-active gene is called thalassaemic and thereby the haematological picture: thalassaemia.

The defects of the globin genes not only strike the β gene but also the α, γ and δ genes. The most important varieties are however the β thalassaemias causing in specific genetic conditions the Mediterranean anaemia, while the α thalassaemias, also being very more frequent than the β thalassaemias, cause a less serious clinical picture and, only in some countries of the southeast Asian, a deadly illness (hydrops ascites foetal).

Defects of the globin genes causing thalassaemia

The DNA studies of the globin genes has not only shown the exact disposition of the α and non-α globin genes on the chromosomes 16 and 11, respectively but also the existence of numerous varieties (by now around 300) of α, β, δ and γ thalassaemias, that is added to those in precedence already identified through the alterations of the haematological-haemoglobin picture.

The thalassaemic defects on the globin genes can be caused by:

• deletions that remove one or more genes of a cluster;
• point mutations that strikes one or few nucleotides of the DNA, alter the transcript of the globin DNA, or alters the pre-mRNA maturation process (processing), causing more often splicing defects that is the release process of the introns;
• non-sense or frameshift mutations, that cause a total arrest of the mRNA translation and therefore a total absence of the dependent globin synthesis;
• mutations that give origin to strongly unstable globin chains, causing a precocious destruction of the erythrocytes.