Hemoglobin Q-Thailand related disorders: origin, molecular, hematological and diagnostic aspects.
We describe the molecular and hematological profiles of thalassemia syndromes caused by interactions of hemoglobin (Hb) Q-Thailand [α74(EF3) Asp-His] and various hemoglobinopathies found in 52 unrelated adult Thai subjects. Ten genotypes including several previously undescribed conditions were observed, which were classified into 4 groups. Group I included 26 Hb Q-Thailand heterozygotes and a homozygotous subject. Group II included subjects with Hb Q-Thailand and other α-thalassemia alleles in trans including 1 compound Hb Q-Thailand/α(+)-thalassemia (-α(3.7)), 2 Hb Q-Thailand/Hb Constant Spring disease and 6 Hb H/Q-Thailand disease. The average levels of Hb Q-Thailand were found to be 29.8%, 82.3%, 34.7%, 49.2-49.3% and 79.4%, respectively. Both Hbs Bart's and H were observed in addition to Hb Q-Thailand in all 6 cases with Hb Q-H disease but not in a homozygous Hb Q-Thailand. Group III included 7 double heterozygotes for Hb Q-Thailand/Hb E, 3 Hb Q-Thailand/Hb E/α(+)-thalassemia (-α(3.7)), 3 heterozygous Hb Q-Thailand/homozygous Hb E and 1 triple heterozygote for Hb Q-Thailand/Hb Constant Spring/Hb E. In this group, Hbs E (α(A)(2)β(E)(2)), Q-Thailand (α(QT)(2)β(A)(2)) and QE (α(QT)(2)β(E)(2)) were observed on both HPLC and capillary electrophoresis. The Hb QE, rather than Hb Q-Thailand, was detected in all 3 cases with heterozygous Hb Q-Thailand and homozygous Hb E. The remaining two cases in group 4 were double heterozygotes for Hb Q-Thailand and β(0)-thalassemia in which Hb Q-Thailand, elevated Hb A(2) (α(A)(2)δ(2)), and Hb QA(2) (α(QT)(2)δ(2)) were detected. DNA analysis identified the Hb Q-Thailand mutation (α74: GAC-CAC) and the linked (-α(4.2)) in all cases. Analysis of α-globin gene haplotype provided the first evidence of a single origin of this Hb variant in Thai population.
Singsanan
Sanita
S
The Graduate School, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Karnpean
Rossarin
R
Fucharoen
Goonnapa
G
Sanchaisuriya
Kanokwan
K
Sae-Ung
Nattaya
N
Fucharoen
Supan
S
D000328:Adult; D000483:Alleles; D019075:Electrophoresis, Capillary / Q000379:methods; D005260:Female; D006446:Hemoglobin E / Q000031:analogs & derivatives / Q000032:analysis / Q000235:genetics; D006447:Hemoglobin H / Q000032:analysis / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000032:analysis* / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D017085:alpha-Thalassemia / Q000097:blood / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D006442:Glycated Hemoglobin
D006446:Hemoglobin E; D006447:Hemoglobin H; D006455:Hemoglobins, Abnormal; C032271:glycated hemoglobin E; D006442:Glycated Hemoglobin; C049214:hemoglobin Q Thailand; C030448:hemoglobin Bart's; C035541:Hemoglobin Constant Spring