An alpha-globin gene initiation codon mutation in a black family with HbH disease.

The molecular basis of hemoglobin H disease in a Black family of Canadian origin was investigated. Affected individuals had a combination of deletion and nondeletion a-thalassemia mutations on different chromosomes. Cloning and sequencing of the DNA of one member with the nondeletion form revealed a new thalassemia mutation, an A – G substitution. in the initiation codon of the remaining a-globin gene of a rightward ( -a37) deletion chromosome. This mutation abolished an Ncol restriction site and therefore is detectable in genomic DNA by Southern blot analysis.