Is Abnormal mRNA Processing Responsible for the Low Percentage of Variants at Residue 27 of the Human α Chain?

Abstract

Mutants of the α chain commonly are present to the extent of 20-25% of a heterozygote's hemoglobin. A major exception is Hb Fort Worth (α₂^{27(β8)Glu→Gly}β₂) which was first identified in a Black family by Schneider et al. (1) and has now been reported by Carstairs et al. (2) in a second Black family. In all heterozygotes, this variant accounts for only 4-5% of the total hemoglobin. As Carstairs et al. note, “The reason for the low quantity of Hb Fort Worth in heterozygotes (4-5%) remains unclear.” Perhaps, in a manner analogous to Hb E, abnormal mRNA processing may be responsible.