Association of Hb Q-Thailand with homozygous Hb E and heterozygous Hb Constant Spring in pregnancy

Abstract

Hemoglobin (Hb) Q-Thailand [α74(EF3): Asp → His] is an abnormal Hb found mainly in China and South-east Asian countries. Association of the αQ-Thailand allele with α-thalassemia has important implications in diagnosis. We report the hitherto undescribed conditions of this variant in two unrelated pregnant Thai women. Routine Hb analyses using high-performance liquid chromatography identified abnormal Hb migrating after Hb A2 in addition to a homozygous Hb E in the proband 1 and to a heterozygous Hb Constant Spring (Hb CS) in the proband 2. Further α-globin gene analysis identified that the variant was caused by the GAC to CAC mutation at codon 74 of the α1-globin gene corresponding to the Hb Q-Thailand, detected in cis to the 4.2 kb deletional α-thalassemia 2 in both cases. Interaction of the αQ-Thailand with the βE globin chains in the proband 1 leads to a Hb variant, namely the Hb QE. Family study of the proband 1 showed that her non-pregnant sister had the same genotype but her father was a double heterozygote for Hb E and Hb Q-Thailand in whom both Hb Q-Thailand and Hb QE were detected. Genotype-phenotype relationships observed in these families with complex hemoglobinopathies are presented and compared with those of simple homozygote for Hb E, heterozygote for Hb CS and heterozygote for Hb Q-Thailand found in other unrelated subjects. A simple DNA assay based on allele-specific polymerase chain reaction for simultaneous detection of the Hb Q-Thailand mutation and the 4.2 kb deletional α-thalassemia 2 determinant was developed and validated.