Nondeletional Hb Queens Park [α32(B13)Met→Lys]/Hb H (β4) Disease

Sroymora, Suravee; Jindadamrongwech, Sumalee; Butthep, Punnee; Chuncharunee, Suporn

doi:10.3109/03630269.2012.658939

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Subsequently, this variant was also identified in parallel as Hb Queens Park. [10] Similar to the early report, we failed to demonstrate the presence of this variant using chromatography and IEF to confirm the unstable nature of this α-hemoglobinopathy [10,21]. However, the phenotype in our patient was mild and never required specific care suggesting that such an unstable variant from the less expressed α1-globin genes might be innocuous in contrast to Hb Pak Num Po (codon 131/T insertion) the related unstable α-globin chains of which cause severe transfusion-dependent Hb H disease [6].…”

Section: Resultsmentioning

confidence: 57%

Clinical Presentation and Molecular Identification of Four Uncommon Alpha Globin Variants in Thailand

Viprakasit¹,

Ekwattanakit²,

Chalaow³

et al. 2013

Acta Haematol

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Alpha thalassemia is the most common genetic disease in the world with the prevalence of carriers ranging from 5-50% in several populations. Coinheritance of two defective α-globin genes usually gives rise to a symptomatic condition, hemoglobin (Hb) H disease. Previously, it has been suggested from several studies in different populations that nondeletional Hb H disease (--/α^Tα or --/αα^T) is generally more severe than the deletional type (--/-α). In this report, we describe four rare nondeletional α-thalassemia mutations in Thai individuals, including initiation codon mutation (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens Park (HBA1:c.98T>A) [α32(B13)Met>Lys], and Hb Westmead (HBA2:c.369C>G) [α122(H5)His>Gln]. Interactions of the first three mutations with the α⁰-thalassemia resulted in nondeletional Hb H disease; however, their clinical presentations were rather mild and some were detected accidentally. This suggests that a genotype-phenotype correlation of α-thalassemia syndrome might be more heterogeneous and so the type of mutation does not simply imply the prediction of the resulting phenotype. Our data will be of use in future genetic counseling of such conditions that are increasingly identified thanks to the improvement of molecular analysis in routine laboratories.

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Section: Resultsmentioning

confidence: 57%

Clinical Presentation and Molecular Identification of Four Uncommon Alpha Globin Variants in Thailand

Viprakasit¹,

Ekwattanakit²,

Chalaow³

et al. 2013

Acta Haematol

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“…Hb Queens Park has been reported originally in a patient of Western Australia with a mild thalassemia phenotype [ 30 ]. Association of Hb Queens Park with α 0 -thalassemia (SEA deletion) led to the non-deletional Hb H disease in a Thai boy with a mild clinical phenotype comparable to that of the common deletional Hb H disease [ 31 ]. Herein described is for the first time Hb Queens Park was identified in association with Hb E in the fetus and with α 0 -thalassemia (SEA deletion) and Hb E trait, leading to the Hb Queens Park AEBart’s disease in the mother who demonstrated a thalassemia intermedia phenotype (Fig.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of fetal hemoglobin Bart’s for evaluation of fetal α-thalassemia syndromes: application to prenatal characterization of fetal anemia caused by undiagnosed α-hemoglobinopathy

Singha

Yamsri

Chaibunruang

et al. 2022

Orphanet J Rare Dis

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Background To evaluate whether the quantification of fetal hemoglobin (Hb) Bart’s is useful for differentiation of α-thalassemia syndromes in the fetus and to characterize the fetal anemia associated with fetal α-hemoglobinopathy. Methods A total of 332 fetal blood specimens collected by cordocentesis were analyzed using capillary electrophoresis and the amount of Hb Bart’s was recorded. The result was evaluated against thalassemia genotypes determined based on Hb and DNA analyses. Prenatal Hb and DNA characterization of the fetal anemia observed in two families was done. Results Among 332 fetuses investigated, Hb and DNA analyses identified 152 fetuses with normal genotypes. The remaining 180 fetuses carried α-thalassemia with several genotypes. Variable amounts of Hb Bart’s were identified in all fetuses with α-thalassemia, which could be used for simple differentiation of fetal α-thalassemia genotypes. These included α+- and α0-thalassemia traits, homozygous α+-thalassemia and Hb Constant Spring (CS), Hb H disease, Hb H-CS and Hb H-Quong Sze diseases, homozygous α0-thalassemia causing the Hb Bart’s hydrops fetalis and a remain uncharacterized α-thalassemia defect. The previously undescribed interactions of Hb Queens Park and Hb Amsterdam A1 with Hb E were detected in two fetuses with Hb Bart’s of 0.5%. The Hb Queens Park-AEBart’s disease was also noted in one pregnant woman. Prenatal analysis of the fetuses with severe fetal anemia and cardiomegaly with Hb Bart’s of 9.0% and 13.6% revealed unexpectedly the homozygous Hb CS and a compound heterozygosity of Hb CS/Hb Pakse’ with Hb E heterozygote, respectively. Conclusions The usefulness of detecting and differentiation of fetal α-thalassemia syndromes by quantifying of Hb Bart’s was demonstrated. Apart from the fatal condition of Hb Bart’s hydrops fetalis associated with homozygous α0-thalassemia, homozygous Hb CS and a compound Hb CS/Hb Pakse’ could result in severe fetal anemia and fetal complications, prenatal diagnosis is highly recommended. The simple Hb Bart’s quantification of fetal blood should prove helpful in this matter.

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“…However, there are a number of Hb variants, which when coexisting with thalassemia, other variants, or in a homozygous form can cause anemia. For examples, Hb E (HBB: exon 1, codon 26 G>A), Hb S (HBB: exon 1, codon 6 A>T), Hb Constant Spring (Hb CS; HBA2: exon 3, codon 142 T>C), Hb Pakse (HBA2: exon 3, codon 142 TAA > TAT), and Hb Queen's Park (HBA1: exon 2, codon 32 T>A) occurring with thalassemia result in increase of clinical severity . Common variants, such as Hb E, Hb CS, and Hb Pakse, present in Thailand are routinely detected by Hb typing and PCR‐based method using sequence‐specific primers, but rare variants are not included in these primer sets and their identification requires DNA sequencing.…”

Section: Introductionmentioning

confidence: 99%