Hb Bart's in Cord Blood: An Accurate Indicator of α-Thalassemia

Abstract

We quantified Hb Bart's (γ4) levels by high performance liquid chromatography (HPLC) in 103 fresh cord blood samples from Homerton Hospital, East London, UK. The α-globin gene arrangement was determined by Southern blot hybridization and genomic sequence analysis of the α-globin genes. The cord blood Hb Bart's levels ranged from 0.5 to 11.9% of total hemoglobin (Hb) and were arranged into three categories: i) levels below 1.5%; ii) levels between 1.5 and 5.7%; iii) levels above 6.1%. These corresponded to a normal α-globin genotype, a single deleted/inactivated α-globin gene and two deleted/inactivated α-globin genes, respectively. The study identified the 3.7 kb and 20.5 kb α-thalassemia (thal) deletions, three non deletional α-thal mutations and a novel α-globin gene rearrangement. Hb Bart's screening of fresh umbilical cord blood is an effective method to evaluate globin chain imbalance. This strategy could be utilized to screen populations for the incidence of α-thal and also to identify rare or new molecular lesions that reduce α-globin gene expression.