The distribution of the Hb Constant Spring gene in Southeast Asian populations

Laig, Marion; Pape, M.; Hundrieser, J.; Flatz, G.; Sanguansermsri, Torpong; Das, Bhuban Mohan; Deka, Ranjan; Yongvanit, Puangrat; N, Mularlee

doi:10.1007/bf00208939

Cited by 54 publications

(32 citation statements)

References 11 publications

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“…Hemoglobin Constant Spring (HbCS), usually seen in Asian populations, is characterized by an elongated a chain with additional 31 amino acid residues, caused by a point mutation in the termination codon of the a2-globin gene (HBA2 c.427T [ C) [25,26]. HbCS was detected in two patients for the first time in Turkey.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

Bozdoğan

Yüreğir

Büyükkurt

et al. 2014

Indian J Hematol Blood Transfus

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To look over the distribution of the mutations in a large series from Adana province, Southern Turkey, and determine the genotype-phenotype correlation of the frequent mutations. Among the 2500 individuals with mild or moderate anemia, microcytosis, and normal iron levels that were referred to our Genetic Diagnosis Center, a population consisting of 539 individuals were included in the study and tested for alpha-thalassemia mutations by using reverse dot blot hybridization technique. Twelve different mutations were detected in 539 patients. Among the 12 different mutations found, the most frequent mutations were the -a 3.7 (63.3 %), -MED (11.7 %), -20.5 (10.7 %), a2 IVS1(-5nt) (3.9 %), and a2 polyA-2 (3.5 %). The most frequent genotypes were -a 3.7 /aa (35.8 %), -a 3.7 /-a 3.7 (18.9 %), -20.5 /aa (11.5 %), and -MED /aa (10.4 %), respectively. There were statistically significant differences in hematological findings between -a 3.7 /-a 3.7 and -MED /aa, even though both have two mutated genes in the genotype. Our results show that alpha-thalassemia mutations are highly heterogeneous as well as deletional and -a 3.7 single gene deletion is particularly prevalent at Adana province in agreement to other studies from Turkey.

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Section: Discussionmentioning

confidence: 99%

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

Bozdoğan

Yüreğir

Büyükkurt

et al. 2014

Indian J Hematol Blood Transfus

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“…This shift reflects selective destabilization of most nonglobin mRNAs and reciprocal stabilization of globin mRNAs (47). Loss of ␣-globin mRNA stability due to mutations in the ␣-globin gene results in a common form of ␣-thalassemia (␣Constant Spring) (10,24). Thus, robust expression of globins is dependent on gene transcription early in the differentiation process and selective stabilization of globin mRNAs late in the process.…”

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confidence: 99%

The 3′ Untranslated Region Complex Involved in Stabilization of Human α-globin mRNA Assembles in the Nucleus and Serves an Independent Role as a Splice Enhancer

Ji¹,

Kong²,

Carstens

et al. 2007

Molecular and Cellular Biology

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Posttranscriptional controls, mediated primarily by RNA-protein complexes, have the potential to alter multiple steps in RNA processing and function. Human ␣-globin mRNA is bound at a C-rich motif in the 3 untranslated region (3UTR) by the KH domain protein ␣-globin poly(C)-binding protein (␣CP). This "␣-complex" is essential to cytoplasmic stability of ␣-globin mRNA in erythroid cells. Here we report that the 3UTR ␣-complex also serves an independent nuclear role as a splice enhancer. Consistent with this role, we find that ␣CP binds ␣-globin transcripts prior to splicing. Surprisingly, this binding occurs at C-rich sites within intron I as well as at the 3UTR C-rich determinant. The intronic and 3UTR ␣CP complexes appear to have distinct effects on splicing. While intron I complexes repress intron I excision, the 3UTR complex enhances splicing of the full-length transcript both in vivo and in vitro. In addition to its importance to splicing, nuclear assembly of the 3UTR ␣CP complex may serve to "prepackage" ␣-globin mRNA with its stabilizing complex prior to cytoplasmic export. Linking nuclear and cytoplasmic controls by the action of a particular RNA-binding protein, as reported here, may represent a modality of general importance in eukaryotic gene regulation.Posttranscriptional controls are central to the establishment and regulation of eukaryotic gene expression (15,35). Recent data highlight critical links between nuclear and cytoplasmic processes involved in these regulatory pathways. Three prominent examples illustrate how the "nuclear history" of a transcript can affect its fate in the cytoplasm. (i) Translational activity of maternal mRNAs in Xenopus oocytes reflects whether precursor transcripts have transited the nuclear splicing pathway (32). More recent studies demonstrate the same relationship in mammalian cells (4,36,37,52). The mechanism(s) that links nuclear splicing and cytoplasmic translational activity remains poorly defined. (ii) Accelerated cytoplasmic destruction of mRNAs containing premature termination codon-containing mRNAs (nonsense-mediated mRNA decay) is dependent upon the position of the premature termination codon relative to exon-exon junctions (16, 28). This nuclear "history" (i.e., where introns were located) is recorded by deposition of a multiprotein exon-junction complex at the site of each splice (16,26,53). (iii) A specific subset of cytokine mRNAs are stabilized in the cytoplasm by binding of hnRNP D p37 to a 3Ј untranslated region (3ЈUTR) AU-rich motif. Remarkably, the formation of this 3ЈUTR RNP occurs exclusively in the nucleus prior to mRNA export (7). Thus, nuclear import of a shuttling RNA-binding protein can be a prerequisite for its deposition on target transcripts and subsequent stabilization of an mRNA(s) in the cytoplasm (7). While the overall impact of "nuclear history" on the cytoplasmic fate of specific mRNAs is evident based on these and other examples (27, 43), the underlying mechanisms involved in integrating these controls and the degree to which they c...

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“…This abnormal hemoglobin results from point mutation at the stop codon of a2-globin gene (TAA?CAA) which leads to the addition of 31 amino acids to normal a-globin sequence [1,2]. The heterozygote of Hb CS is clinically and hematologically normal.…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis

Pornprasert

Saoboontan

Wiengkum³

2015

Indian J Hematol Blood Transfus

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Hemoglobin Constant Spring [Hb CS; a142, Term?Gln (TAA[CAA IN a2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of b-thalassemia or b-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of a-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [b26 (B8) Glu?Lys, GAG[AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

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The distribution of the Hb Constant Spring gene in Southeast Asian populations

Cited by 54 publications

References 11 publications

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

The 3′ Untranslated Region Complex Involved in Stabilization of Human α-globin mRNA Assembles in the Nucleus and Serves an Independent Role as a Splice Enhancer

Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis

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