The understanding of the phenotypic variability of genetically homogenous disorders represents a major challenge. In ß-thalassaemia the ß-globin gene is affected by a variety of mutations. The group of patients to be analyzed here is homozygous for a splice site mutation that is common in the Middle East. In contrast to this genetic homogeneity the spectrum of the clinical phenotype ranges from mild anaemia to most severe, transfusion-dependent anaemia. We aim at an understanding of this perplexing clinical variability by using a genetic linkage approach to identify modifying factors and by analyzing the efficiency of an mRNA surveillance mechanism that is referred to as nonsense-mediated decay and represents a candidate genetic modifier of ß-thalassaemia and other genetic disorders.