The most common cause of beta thalassemia

The  mutations  responsible  for  β-thalassemia  disrupt β-globin synthesis in several different ways Mutations  leading  to  aberrant  RNA  splicing  are the most common cause of β-thalassemia. Some of these mutations disrupt the normal RNA splice junctions; as a result, no mature mRNA is made and there is a  complete  failure  of  β-globin  production,  creating  β 0 . Other mutations create new splice junctions in abnormal positions—within  an  intron,  for  example.  Because  the normal splice sites are intact, both normal and abnormal splicing occurs, and some normal β-globin mRNA is made. These alleles are designated β + . Some  mutations  lie  within  the  β-globin  promoter  and lower  the  rate  of  β-globin  gene  ranscription.  Because some normal β-globin is synthesized, these are β +  alleles. Other  mutations  involve  the  coding  regions  of  the  β-globin  gene,  usually  with  severe  consequences.  For example, some single-nucleotide changes create termination  (“stop”)  codons  that  interrupt  the  translation  of β-globin mRNA and completely prevent the synthesis of β-globin.