Hb A2 Hong Kong - A novel δ-globin variant in a chinese family masks the diagnosis of β-thalassemia trait

A 42-year-old Chinese woman (FP) was the mother of a patient with β-thalassemia major (β-TM) due to a compound heterozygosity for β 0-thalassemia (β 0-thal) mutations. She was also found to have a low Hb A2 level of 1.6% by high performance liquid chromatography (HPLC) despite being a heterozygous carrier of the codons 41/42 (-TCTT) (HBB:c.126-129delCTTT) β 0-thal mutation. Doubling the amount of hemolysate loaded for chromatography revealed a widened Hb A2 peak and raised the level to 4.1%, consistent with β-thal trait. Direct nucleotide sequencing detected a novel δ-globin gene mutation at codon 29 (HBD:c.89G>A), which leads to a glycine to aspartic acid substitution. A homologous mutation at codon 29 in the β-globin gene [Hb Lufkin or β29(B11)Gly→Asp] has been reported in Black families. This report highlights the importance of genotype-phenotype correlation and the potential pitfall of relying on Hb A2 level for phenotypic diagnosis of β 0-thal trait. © 2011 Informa Healthcare USA, Inc.link_to_subscribed_fulltex