Hb A2 Hong Kong - A Novel δ-Globin Variant in a Chinese Family Masks the Diagnosis of β-Thalassemia Trait

• Published in: Hemoglobin 2011-04, Vol.35 (2), p.162-165
• Main Authors: So, Chi-Chiu, Chan, Amy Y.Y., Luo, Hong-Yuan, Verhovsek, Madeleine, Chui, David H.K., Ling, Siu-Cheung, Chan, Li-Chong
• Format: Article
• Language: English
• Subjects: Adult; Base Sequence; beta-Thalassemia - diagnosis; beta-Thalassemia - genetics; China; Chinese; Codon; delta-Globins - genetics; Female; Hemoglobin A2 - genetics; Humans; Masked β-thalassemia (β-thal); Mutation, Missense - genetics; δ-Globin variant
• ISSN: 0363-0269; 1532-432X
• DOI: 10.3109/03630269.2011.557172

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 β0-thalassemia (β0-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) β0-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 β0-thal trait.