title: Hb A2 Hong Kong - A novel δ-globin variant in a Chinese family masks the diagnosis of β-thalassemia trait.
abstract: 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 A(2) 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 A(2) 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 A(2) level for phenotypic diagnosis of β(0)-thal trait.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China. scc@pathology.hku.hk
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: So
authors.forename: Amy Y Y
authors.initials: AY
authors.lastname: Chan
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Luo
authors.forename: Madeleine
authors.initials: M
authors.lastname: Verhovsek
authors.forename: David H K
authors.initials: DH
authors.lastname: Chui
authors.forename: Siu-Cheung
authors.initials: SC
authors.lastname: Ling
authors.forename: Li-Chong
authors.initials: LC
authors.lastname: Chan
mesh_terms: D000328:Adult; D001483:Base Sequence; D002681:China; D003062:Codon; D005260:Female; D006443:Hemoglobin A2 / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics*; D055546:delta-Globins / Q000235:genetics*
chemical_list: D003062:Codon; D055546:delta-Globins; D006443:Hemoglobin A2