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

Abstract

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.

Detection of Compound Heterozygous of Hb Constant Spring and Hb Q-Thailand by Capillary Electrophoresis and High Performance Liquid Chromatography

“…Peak of Hb H and Hb Bart's were not found on HPCL and CE analysis. The previous studies showed that patients with compound heterozygous of Hb CS and Hb Q-Thailand had mild hypochomic microscytic anemia [4,15] and it was consistent with the present study which showed that a patient had low levels of Hb and MCV. However, patients in the present study had a higher MCV than the patients with the compound heterozygous of Hb CS and Hb Q-Thailand who were reported by Singsanan et al, and it was quite similar to the MCV of 26 patients with heterozygous of Hb Q-Thailand [4].…”

“…The molecular analysis for detection of a-thalassemia-1 Southeast Asian (SEA) type deletion and Hb CS was performed by using real-time PCR with SYBR Green1 high resolution melting (HRM) analysis as previously described [13,14]. The multiple allele specific polymerase chain reaction (ASPCR) was also performed for molecular diagnosis of Hb Q-Thailand as previously described [4,15].…”

Molecular Heterogeneity of Thalassemia among Pregnant Laotian Women

“…Globin gene mutations causing high Hb F levels, including δβ thalassemia, HPFH-6, and deletion-inversion G γ( A γδβ) 0 -thalassemia, were also investigated in suspected cases. Polymerase chain reaction (PCR) techniques as described previously (either Gap PCR or allele-specific PCR) were used for DNA analysis [12][13][14][15][16][17] .…”

Five Hemoglobin Variants in a Double Heterozygote for α- and β-Globin Chain Defects

“…In fact, it is not unexpected that tetrameric assembly of these globin chain variants could generate some uncommon Hb variants which might complicate laboratory diagnostics. Interactions of the α Q-Thailand -globin chain with β A -, β E -, δ-, and γ-globin chains subsequently lead to the formation of Hb Q-Thailand (α QT 2 β A 2 ), Hb QE (α QT 2 β E 2 ), Hb QA 2 (α QT 2 δ 2 ), and Hb QF (α QT 2 γ 2 ), respectively, with different HPLC and capillary electrophoretic profiles [9,13,14,15]. As shown in figure 1, we detected as many as 5 Hb variants in the two Thai patients with double heterozygosity for Hb Q-Thailand and Hb Tak, including Hb Q-Thailand (α QT 2 β A 2 ), Hb Tak (α A 2 β Tak 2 ), Hb QA 2 (α QT 2 δ 2 ), Hb QF (α QT 2 γ 2 ), and a novel variant, i.e.…”