A NOVEL DELTA-DEGREES MUTATION IN CIS WITH HB KNOSSOS - A STUDY OF DIFFERENT GENETIC INTERACTIONS IN 3 EGYPTIAN FAMILIES

We have defined the molecular basis of normal HbA2 beta-thalassaemia associated with Hb Knossos. DNA sequence analysis of the delta-globin gene in cis with beta-Knossos showed deletion of a single A in codon 59 leading to a premature termination at codon 60. This delta-degrees/beta-Knossos allele has been observed in three unrelated Egyptian families and associated with a single beta-haplotype (+ - - - - + +). One individual who was homozygous for the delta-degrees/beta-Knossos allele as well as heterozygous for a non-deletional-alpha-thalassaemia, was completely clinically asymptomatic, while others have co-inherited the delta-degrees/beta-Knossos allele with different-beta and alpha-thalassaemia determinants. A study of the different genetic interactions giving rise to a spectrum of clinical phenotypes is reported.