Association of Hb Q-Thailand with homozygous Hb E and heterozygous Hb Constant Spring in pregnancy.
Hemoglobin (Hb) Q-Thailand [alpha74(EF3): Asp-->His] is an abnormal Hb found mainly in China and South-east Asian countries. Association of the alpha(Q-Thailand) allele with alpha-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 A(2) 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 alpha-globin gene analysis identified that the variant was caused by the GAC to CAC mutation at codon 74 of the alpha1-globin gene corresponding to the Hb Q-Thailand, detected in cis to the 4.2 kb deletional alpha-thalassemia 2 in both cases. Interaction of the alpha(Q-Thailand) with the beta(E) 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 alpha-thalassemia 2 determinant was developed and validated.
Sanchaisuriya
Kanokwan
K
The Graduate School, Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Chunpanich
Sunisa
S
Fucharoen
Supan
S
Fucharoen
Goonnapa
G
Sanchaisuriya
Pattara
P
Changtrakun
Yossombat
Y
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics; D006446:Hemoglobin E / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D009154:Mutation; D011247:Pregnancy; D013785:Thailand
D006455:Hemoglobins, Abnormal; C049214:hemoglobin Q Thailand; D005914:Globins; D006446:Hemoglobin E; C035541:Hemoglobin Constant Spring