A New Hb Evanston Allele [α14(A12)Trp → Arg] Found Solely, and in the Presence of Common α‐Thalassemia Deletions, in Three Independent Asian Cases

Abstract

Hb Evanston [α14(A12)Trp → Arg] is considered to be a rare α chain mutant, and was originally observed in two Black families in 1982, inducing a mild Hb H disease phenotype in a homozygous state for the − α^3.7 deletion ( − α^Evanston/ − α). The mutant, evidently linked with one of the two − α^3.7 thalassemia (thal) alleles, was considered to be unstable and rapidly proteolyzed. We describe Hb Evanston in three new independent Asian cases, all induced by a TGG → CGG transition. In all cases the mutation is linked to the α1‐globin gene, either on a wild type allele or in linkage with the common − α^3.7 and − α^4.2 deletion alleles. The β/α ratio was balanced in the presence of the mutation only, and accordingly unbalanced in co‐inheritance with the deletion defects. Although a second independent mutation event on a − α^3.7 or a − α^4.2 deletion allele could not be excluded, we conclude that at least one independent Hb Evanston mutation has occurred on a wild type allele in the Asian populations. Unstable Hb tetramers tend to degrade and disappear during purification. Both Hb Evanston tetramers, formed in combination with normal β and δ chains, remain perfectly stable after extensive purification and concentration steps, suggesting an early posttranslational thalassemic effect, probably at the dimer/tetramer affinity level.

• Hb Evanston
• α‐Globin
• α‐Thalassemia (thal)
• Deletion