Pranee Winichagoon

Publications (60)138.46 Total impact

• Article: A reduced curcuminoid analog as a novel inducer of fetal hemoglobin.

  Nattawara Chaneiam, Chatchawan Changtam, Thongperm Mungkongdee, Umaporn Suthatvoravut, Pranee Winichagoon, Jim Vadolas, Apichart Suksamrarn, Suthat Fucharoen, Saovaros Svasti
  [show abstract] [hide abstract]
  ABSTRACT: Thalassemia is an inherited disorder of hemoglobin molecules that is characterized by an imbalance of α- and β-globin chain synthesis. Accumulation of unbound α-globin chains in erythroid cells is the major cause of pathology in β-thalassemia. Stimulation of γ-globin production can ameliorate disease severity as it combines with the α-globin to form fetal hemoglobin. We examined γ-globin-inducing effect of curcuminoids extracted from Curcuma longa L. and their metabolite reduced forms in erythroid leukemia K562 and human primary erythroid precursor cells. The results showed that curcuminoid compounds, especially bisdemethoxycurcumin are potential γ-globin enhancers. We also demonstrated that its reduced analog, hexahydrobisdemethoxycurcumin (HHBDMC), is most effective and leads to induction of γ-globin mRNA and HbF in primary erythroid precursor cells for 3.6 ± 0.4- and 2.0 ± 0.4-folds, respectively. This suggested that HHBDMC is the potential agent to be developed as a new therapeutic drug for β-thalassemia and related β-hemoglobinopathies.
  Annals of Hematology 10/2012; · 2.62 Impact Factor
• Article: Quantitative analysis of Hb Bart’s in cord blood by capillary electrophoresis system

  Thongperm Munkongdee, Dalad Pichanun, Punnee Butthep, Sumonmaln Klamchuen, Veeradet Chalermpolprapa, Pranee Winichagoon, Saovaros Svasti, Suthat Fucharoen
  [show abstract] [hide abstract]
  ABSTRACT: It has long been recognized that the presence of hemoglobin (Hb) Bart’s in newborn’s blood is associated with α-thalassemia. However, the automated high-performance liquid chromatography or low-performance liquid chromatography system is unable to quantify the amount of Hbs Bart’s and H, which are eluted at the retention time close to 0min. This study used automatic capillary electrophoresis (CE) system to diagnose various types of α-thalassemia in 587 cord blood samples, including 429 normal α-globin genotype, 120 cases of thalassemia with one α-globin gene defect, 34 cases with two α-globin genes defect, and four cases with three α-globin genes defect. The result showed that the level of Hb Bart’s in cord blood was increased accordingly with the increasing numbers of the defective α-globin genes. In addition, Hb Bart’s level at 0.2%, as measured by CE, can be used as a cut-off point for α-thalassemia diagnosis in newborns. Keywordsα-Thalassemia–Hemoglobin Bart’s–Capillary electrophoresis
  Annals of Hematology 04/2012; 90(7):741-746. · 2.62 Impact Factor
• Article: Noninvasive Prenatal Diagnosis for Hemoglobin Bart’s Hydrops Fetalis

  Pranee Winichagoon, Saisiri Sithongdee, Sujin Kanokpongsakdi, Pornpen Tantisirin, Luigi F. Bernini, Suthat Fucharoen
  [show abstract] [hide abstract]
  ABSTRACT: Hemoglobin (Hb) Bart’s hydrops fetalis, the most severe thalassemic disease, occurs from homozygosity of α-thalassemia 1. Deletion of all 4 α-globin genes (- -/- -) in this condition results in the absence of α-globin chains, and the physiologic dysfunction of Hb Bart’s (γ4) leads to lethality, either in utero or soon after birth. The best strategy for prevention and control of the disease is prenatal diagnosis in the mothers at risk. However, conventional prenatal diagnosis involves invasive procedures that may result in infection or abortion. In this study, a simple technique was developed to identify the presence or absence of α-globin chains in fetal nucleated red blood cells (NRBCs) enriched from maternal blood. Mononuclear cells including fetal NRBCs were isolated from maternal blood at 10 to 26 weeks of pregnancy by density-gradient centrifugation. Immunomagnetic separation with anti-CD71 antibody was employed to enrich fetal NRBCs, whose numbers increase with increasing gestational age. For the unaffected fetus, fetal NRBCs were detected by immunofluorescence microscopy after staining with rabbit antihuman α-globin antibody. In contrast, fetal red blood cells homozygous for α-thalassemia 1, which were identified from their size and morphology, did not stain for a-globin antibody. In this study, 3 affected fetuses were detected from 10 pregnancies at risk of Hb Bart’s hydrops fetalis, and the results were confirmed by DNA analysis. In the remaining cases, all fetal NRBCs were positive for immunofluorescence staining. DNA analysis revealed that 2 cases were normal, 1 was heterozygous for α-thalassemia 2, and the other 4 cases were heterozygous for α-thalassemia 1.
  International Journal of Hematology 04/2012; 81(5):396-399. · 1.27 Impact Factor
• Source

  Available from: Manit Nuinoon

  Chapter: Genomic Study in ?-Thalassemia

  Saovaros Svasti, Orapan Sripichai, Manit Nuinoon, Pranee Winichagoon, Suthat Fucharoen
  11/2011; , ISBN: 978-953-307-305-7
• Article: Haemoglobinopathies in southeast Asia.

  Suthat Fucharoen, Pranee Winichagoon
  [show abstract] [hide abstract]
  ABSTRACT: In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous α-thalassaemia 1), homozygous β-thalassaemia, β-thalassaemia/Hb E and Hb H diseases. α-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the β-globin gene sequence are the major molecular defects responsible for most β-thalassaemias. Clinical manifestations of α-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of β-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, β-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous β-thalassaemia. Concomitant inheritance of α-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both α- and β-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies.
  The Indian journal of medical research 10/2011; 134:498-506. · 1.84 Impact Factor
• Article: Molecular analysis of globin gene expression in different thalassaemia disorders: individual variation of β(E) pre-mRNA splicing determine disease severity.

  Alisa Tubsuwan, Thongperm Munkongdee, Natee Jearawiriyapaisarn, Chanikarn Boonchoy, Pranee Winichagoon, Suthat Fucharoen, Saovaros Svasti
  [show abstract] [hide abstract]
  ABSTRACT: Thalassaemia is characterized by the reduced or absent production of globins in the haemoglobin molecule leading to imbalanced α-globin/non α-globin chains. HbE, the result of a G to A mutation in codon 26 of the HBB (β-globin) gene, activates a cryptic 5' splice site in codon 25 leading to a reduction of correctly spliced β(E) -globin (HBB:c.79G>A) mRNA and consequently β(+) -thalassaemia. A wide range of clinical severities in bothα- and β-thalassaemia syndromes, from nearly asymptomatic to transfusion-dependent, has been observed. The correlation between clinical heterogeneity in various genotypes of thalassaemia and the levels of globin gene expression and β(E) -globin pre-mRNA splicing were examined using multiplex quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and allele-specific RT-qPCR. The α-globin/non α-globin mRNA ratio was demonstrated to be a good indicator for disease severity among different thalassaemia disorders. However, the α-globin/non α-globin mRNA ratio ranged widely in β-thalassaemia/HbE patients, with no significant difference between mild and severe phenotypes. Interestingly, the correctly to aberrantly spliced β(E) -globin mRNA ratio in 30% of mild β-thalassaemia/HbE patients was higher than that of the severe patients. The splicing process of β(E) -globin pre-mRNA differs among β-thalassaemia/HbE patients and serves as one of the modifying factors for disease severity.
  British Journal of Haematology 09/2011; 154(5):635-43. · 4.94 Impact Factor
• Article: Quantitative analysis of Hb Bart's in cord blood by capillary electrophoresis system.

  Thongperm Munkongdee, Dalad Pichanun, Punnee Butthep, Sumonmaln Klamchuen, Veeradet Chalermpolprapa, Pranee Winichagoon, Saovaros Svasti, Suthat Fucharoen
  [show abstract] [hide abstract]
  ABSTRACT: It has long been recognized that the presence of hemoglobin (Hb) Bart's in newborn's blood is associated with α-thalassemia. However, the automated high-performance liquid chromatography or low-performance liquid chromatography system is unable to quantify the amount of Hbs Bart's and H, which are eluted at the retention time close to 0 min. This study used automatic capillary electrophoresis (CE) system to diagnose various types of α-thalassemia in 587 cord blood samples, including 429 normal α-globin genotype, 120 cases of thalassemia with one α-globin gene defect, 34 cases with two α-globin genes defect, and four cases with three α-globin genes defect. The result showed that the level of Hb Bart's in cord blood was increased accordingly with the increasing numbers of the defective α-globin genes. In addition, Hb Bart's level at 0.2%, as measured by CE, can be used as a cut-off point for α-thalassemia diagnosis in newborns.
  Annals of Hematology 12/2010; 90(7):741-6. · 2.62 Impact Factor
• Article: Expression of microRNA-451 in normal and thalassemic erythropoiesis.

  Saovaros Svasti, Shizuka Masaki, Tipparat Penglong, Yasunobu Abe, Pranee Winichagoon, Suthat Fucharoen, Tsukuru Umemura
  [show abstract] [hide abstract]
  ABSTRACT: MicroRNAs (miRNAs) are negative regulators of gene expression that play an important role in hematopoiesis. Thalassemia, a defective globin synthesis leading to precipitate of excess unbound globins in red blood cell precursors, results in defective erythroid precursors and ineffective erythropoiesis. Expression pattern of miR-451, an erythroid-specific miRNA, was analyzed during differentiation of erythroid progenitors derived from normal and thalassemic peripheral blood CD34-positive cells, after 14 days of culture. A biphasic expression with transient up-regulation of miRNA-451 on day 3 of cultures was observed during thalassemic erythroid differentiation. In contrast, the expression pattern of the miR-451 in erythroid cells obtained from the other extravascular hemolytic anemia, i.e., hereditary spherocytosis patients showed no transient up-regulation of miR-451 on day 3 of cultures. Our results suggest that early erythroid progenitors in beta-thalassemia have a dysregulated miRNA-451 expression program, and analysis of microRNA is a relevant approach to determine abnormalities of erythropoiesis.
  Annals of Hematology 05/2010; 89(10):953-8. · 2.62 Impact Factor
• Article: A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia/hemoglobin E.

  Manit Nuinoon, Wattanan Makarasara, Taisei Mushiroda, Iswari Setianingsih, Pustika Amalia Wahidiyat, Orapan Sripichai, Natsuhiko Kumasaka, Atsushi Takahashi, Saovaros Svasti, Thongperm Munkongdee, Surakameth Mahasirimongkol, Chayanon Peerapittayamongkol, Vip Viprakasit, Naoyuki Kamatani, Pranee Winichagoon, Michiaki Kubo, Yusuke Nakamura, Suthat Fucharoen
  [show abstract] [hide abstract]
  ABSTRACT: b-Thalassemia/HbE disease is clinically variable. In searching for genetic factors modifying the disease severity, patients were selected based on their disease severities, and a genome-wide association study (GWAS) was performed. Genotyping was conducted with the Illumina Human 610-Quad BeadChips array using DNAs from 618 Thai b0-thalassemia/HbE patients who were classified as 383 severe and 235 mild phenotypes by a validated scoring system. Twenty-three SNPs in three independent genes/regions were identified as being significantly associated with the disease severity. The highest association was observed with SNPs in the b-globin gene cluster (chr.11p15), and rs2071348 of the HBBP1 gene revealed the most significant association [P = 2.96 9 10(-13), odds ratio (OR) = 4.33 (95% confidence interval (CI), 2.74-6.84)]. The second was identified in the intergenic region between the HBS1L and MYB genes (chr.6q23), among which rs9376092 was the most significant [P = 2.36 9 10(-10), OR = 3.07 (95% CI, 2.16-4.38)]. The third region was located in the BCL11A gene (chr.2p16.1), and rs766432 showed the most significant association [P = 5.87 9 10-10, OR = 3.06 (95% CI, 2.15-4.37)]. All three loci were replicated in an independent cohort of 174 Indonesian patients. The associations to fetal hemoglobin levels were also observed with SNPs on these three regions. Our data indicate that several genetic loci act in concert to influence HbF levels of beta(0)-thalassemia/HbE patients. This study revealed that all the three reported loci and the alpha-globin gene locus are the best and common predictors of the disease severity in beta-thalassemia.
  Human Genetics 03/2010; 127(3):303-14. · 5.07 Impact Factor
• Source

  Available from: Lindsay Farrer

  Article: Genetic modifiers of Hb E/beta0 thalassemia identified by a two-stage genome-wide association study.

  Richard Sherva, Orapan Sripichai, Kenneth Abel, Qianli Ma, Johanna Whitacre, Vach Angkachatchai, Wattanan Makarasara, Pranee Winichagoon, Saovaros Svasti, Suthat Fucharoen, Andreas Braun, Lindsay A Farrer
  [show abstract] [hide abstract]
  ABSTRACT: Patients with Hb E/beta0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/beta0 thalassemia and normal alpha-globin genes. First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping. After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the beta-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 x 10(-13)). Seven SNPs in two distinct LD blocks within a region centromeric to the beta-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 x 10(-11)). Several previously unreported SNPs were also significantly associated with disease severity. These results suggest that there may be an additional regulatory region centromeric to the beta-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression.
  BMC Medical Genetics 03/2010; 11:51. · 2.33 Impact Factor
• Article: Rapid diagnosis of alpha-thalassemia by melting curve analysis.

  Thongperm Munkongdee, Phantip Vattanaviboon, Parichut Thummarati, Paijit Sewamart, Pranee Winichagoon, Suthat Fucharoen, Saovaros Svasti
  [show abstract] [hide abstract]
  ABSTRACT: alpha-Thalassemia is an inherited hemoglobin disorder that results from defective synthesis of alpha-globin protein. Couples who both carry the alpha-thalassemia-1 gene are at risk of having a fetus with Hb Bart's hydrops fetalis. Rapid and accurate screening for individuals carrying the alpha-thalassemia-1 gene is the most effective strategy to prevent and control this severe form of thalassemia. In this study, a new and accurate method for alpha-thalassemia diagnosis was developed by genotyping alpha-thalassemia-1, the Southeast Asian type (--(SEA)) and Thai type (--(THAI)) deletions, using multiplex PCR followed by a melting curve analysis. Primers were designed to specifically amplify two deletion fragments, the --(SEA) and --(THAI) deletions and two normal fragments, psizeta- and alpha2-globin gene. The primers were capable of distinguishing alpha-thalassemia 1 heterozygotes from alpha-thalassemia 2 homozygotes, which are unable to be diagnosed by standard hematological data and hemoglobin typing. The melting temperatures of the --(THAI), --(SEA), psizeta-globin, and alpha2-globin gene fragments were 79.9 +/- 0.2, 89.4 +/- 0.5, 92.8 +/- 0.2, and 85.0 +/- 0.2 degrees C, respectively. Melting curve analysis was performed in 130 subjects in parallel with conventional gap-PCR analysis, and results showed 100% concordance. This method eliminates the post-PCR electrophoresis process, which is laborious, and allows high throughput screening suitable for large population screening for prevention and control of thalassemia.
  The Journal of molecular diagnostics: JMD 02/2010; 12(3):354-8. · 3.48 Impact Factor
• Article: Genetic modifiers of Hb E/β⁰thalassemia identified by a two-stage genome-wide association study

  Richard Sherva, Orapan Sripichai, Kenneth Abel, Qianli Ma, Johanna Whitacre, Vach Angkachatchai, Wattanan Makarasara, Pranee Winichagoon, Saovaros Svasti, Suthat Fucharoen, Andreas Braun, Lindsay Farrer
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Background Patients with Hb E/β⁰thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/β⁰thalassemia and normal α-globin genes. Methods First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping. Results After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity ( P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the β-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 × 10^-13). Seven SNPs in two distinct LD blocks within a region centromeric to the β-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 × 10^-11). Several previously unreported SNPs were also significantly associated with disease severity. Conclusions These results suggest that there may be an additional regulatory region centromeric to the β-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression.
  BMC Medical Genetics. 01/2010;
• Article: Molecular screening of the Hbs Constant Spring (codon 142, TAA>CAA, α2) and Paksé (codon 142, TAA>TAT, α2) mutations in Thailand.

  Dalad Pichanun, Thongperm Munkongdee, Sumonmaln Klamchuen, Punnee Butthep, Pranee Winichagoon, Suthat Fucharoen, Saovaros Svasti
  [show abstract] [hide abstract]
  ABSTRACT: Hb Constant Spring [Hb CS, α142(H19)Term] and Hb Paksé [α142(H19)Term] occur from the mutation in the termination codon of the α2-globin gene, TAA>CAA (→Gln) and TAA>TAT (→Tyr), respectively. They are the most common nondeletional α-thalassemia (α-thal) variants causing Hb H disease in Southeast Asia. In this study, 587 cord blood samples were screened for the Hb CS and Hb Paksé mutations by a dot-blot hybridization technique using oligonucleotide probes specific for each mutation. The results showed that the prevalence of Hb CS and Hb Paksé in Central Thailand are 5.80 and 0.51%, respectively, which is in concordance with the results from previous studies.
  Hemoglobin 01/2010; 34(6):582-6. · 1.30 Impact Factor
• Source

  Available from: swu.ac.th

  Article: Effect of human beta-globin bacterial artificial chromosome transgenesis on embryo cryopreservation in mouse models.

  Duangjai Boonkusol, Andras Dinnyes, Tassanee Faisaikarm, Parisatcha Sangsuwan, Nathnapith Pratipnatalang, Mayurachat Sa-Ardrit, Kulnasan Saikhun, Saovaros Svasti, Jim Vadolas, Pranee Winichagoon, Suthat Fucharoen, Yindee Kitiyanant
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of the present study was to investigate the efficiency of embryo cryopreservation for four transgenic (TG) thalassaemic mouse strains, which is a key element of the ongoing gene banking efforts for these high-value animals. Heterozygous TG embryos were produced by breeding four lines of TG males to wild-type (WT) females (C57BL/6J). Intact two-cell embryos were cryopreserved by vitrification in straws using 35% ethylene glycol. Survival rates of cryopreserved embryos ranged between 91.1% (102/112) and 93.6% (176/188) without significant differences between the lines. In contrast, the paternal line had a significant effect on the development of these embryos to the blastocyst stage, which ranged from 50.6% (92/182) to 77.5% (79/102). This effect was also noted following embryo transfers, with implantation rates varying from 17.3% (19/110) to 78.1% (35/45). The results demonstrate that the in vivo developmental potential is significantly influenced by TG line and reveal a specific line effect on cryosurvival. All bacterial artificial chromosome transgenic fetuses developed from vitrified-warmed embryos showed expression of the human beta-globin transgene. In conclusion, the present study shows a strong TG line effect on developmental competence following cryopreservation and the vitrification method was successful to bank the human beta-globin TG-expressing mouse strains.
  Reproduction Fertility and Development 01/2010; 22(5):788-95. · 2.11 Impact Factor
• Article: A genome-wide association identified the common genetic variants influence disease severity in beta(0)-thalassemia/hemoglobin E.

  Manit Nuinoon, Wattanan Makarasara, Taisei Mushiroda, Iswari Setianingsih, Pustika Wahidiyat, Orapan Sripichai, Natsuhiko Kumasaka, Atsushi Takahashi, Saovaros Svasti, Thongperm Munkongdee, Surakameth Mahasirimongkol, Chayanon Peerapittayamongkol, Vip Viprakasit, Naoyuki Kamatani, Pranee Winichagoon, Michiaki Kubo, Yusuke Nakamura, Suthat Fucharoen
  [show abstract] [hide abstract]
  ABSTRACT: beta-Thalassemia/HbE disease is clinically variable. In searching for genetic factors modifying the disease severity, patients were selected based on their disease severities, and a genome-wide association study (GWAS) was performed. Genotyping was conducted with the Illumina Human 610-Quad BeadChips array using DNAs from 618 Thai beta(0)-thalassemia/HbE patients who were classified as 383 severe and 235 mild phenotypes by a validated scoring system. Twenty-three SNPs in three independent genes/regions were identified as being significantly associated with the disease severity. The highest association was observed with SNPs in the beta-globin gene cluster (chr.11p15), and rs2071348 of the HBBP1 gene revealed the most significant association [P = 2.96 x 10(-13), odds ratio (OR) = 4.33 (95% confidence interval (CI), 2.74-6.84)]. The second was identified in the intergenic region between the HBS1L and MYB genes (chr.6q23), among which rs9376092 was the most significant [P = 2.36 x 10(-10), OR = 3.07 (95% CI, 2.16-4.38)]. The third region was located in the BCL11A gene (chr.2p16.1), and rs766432 showed the most significant association [P = 5.87 x 10(-10), OR = 3.06 (95% CI, 2.15-4.37)]. All three loci were replicated in an independent cohort of 174 Indonesian patients. The associations to fetal hemoglobin levels were also observed with SNPs on these three regions. Our data indicate that several genetic loci act in concert to influence HbF levels of beta(0)-thalassemia/HbE patients. This study revealed that all the three reported loci and the alpha-globin gene locus are the best and common predictors of the disease severity in beta-thalassemia.
  Human Genetics 11/2009; · 5.07 Impact Factor
• Article: Two Cases of Compound Heterozygosity for Hb Hekinan [α27(B8)Glu→Asp (α1)] and α‐Thalassemia in Thailand

  Lukana Ngiwsara, Chantragan Srisomsap, Pranee Winichagoon, Suthat Fucharoen, Jisnuson Svasti
  [show abstract] [hide abstract]
  ABSTRACT: Two unrelated cases of compound heterozygosity for Hb Hekinan [α27(B8)Glu→Asp (α1)] and α‐thalassemia have been found in Thailand. Mutations were established at protein level by peptide mapping and at the DNA level by direct sequence analysis. Proband S.S. had genotype – –SEA/α2Aα1Hekinan, βA/βE, while an unrelated proband, S.J., is the first case described with the genotype – –SEA/α2Aα1Hekinan, βA/ βA. Both α1Hekinan mutations were located in the α1 locus. Hb Hekinan could not be accurately estimated by HPLC, since it was poorly separated from Hb A. However IEF gave good separation of Hb Hekinan and Hb A, leading to estimates of Hb Hekinan (α2Hekinan/β2A and α2Hekinan/β2E) level as 40–43% of total Hb.
  08/2009; 28(2):145-150.
• Article: Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic mice.

  Kanitta Srinoun, Saovaros Svasti, Worrakavee Chumworathayee, Jim Vadolas, Phantip Vattanaviboon, Suthat Fucharoen, Pranee Winichagoon
  [show abstract] [hide abstract]
  ABSTRACT: beta-thalassemia occurs from the imbalanced globin chain synthesis due to the absence or inadequate beta-globin chain production. The excessive unbound alpha-globin chains precipitate in erythroid precursors and mature red blood cells leading to ineffective erythropoiesis and hemolysis. In vitro globin chain synthesis in reticulocytes from different types of thalassemic mice was performed. The effect of imbalanced globin chain synthesis was assessed from changes of red blood cell properties including increased numbers of red blood cells vesicles and apoptotic red blood cells, increased reactive oxygen species and decreased red blood cell survival. The alpha/beta-globin chain ratio in beta(IVSII-654)-thalassemic mice, 1.26+/-0.03, was significantly higher than that of wild type mice, 0.96+/-0.05. The thalassemic mice show abnormal hematologic data and defective red blood cell properties. These values were improved significantly in doubly heterozygous thalassemic mice harboring 4 copies of human beta(E)-globin transgene, with a more balanced globin chain synthesis, 0.92+/-0.05. Moreover, transgenic mice harboring 8 extra copies of the human beta(E)-globin transgene showed inversely imbalanced alpha/beta-globin synthesis ratio, 0.83+/-0.01, that resulted in a mild beta-thalassemia phenotype due to the excessive beta-globin chains. The degree of ineffective erythropoiesis also correlated with the degree of imbalanced globin chain synthesis. Bone marrow and splenic erythroid precursor cells of beta(IVSII-654)-thalassemic mice showed increased phosphatidylserine exposure in basophilic and polychromatophilic stages, which was restored to the normal level in doubly heterozygous mice. Imbalanced alpha/beta-globin chain as a consequence of either reduction or enhancement of beta-globin chain synthesis can cause abnormal red blood cell properties in mouse models.
  Haematologica 08/2009; 94(9):1211-9. · 6.42 Impact Factor
• Source

  Available from: Chantragan Srisomsap

  Article: Hb SIAM [α15(A13)Gly → Arg (α1) (GGT → CGT)] IS A TYPICAL α CHAIN HEMOGLOBINOPATHY WITHOUT AN α-THALASSEMIC EFFECT

  Chairat Turbpaiboon, Saovaros Svasti, Phannee Sawangareetakul, Pranee Winichagoon, Chantragan Srisomsap, Noppadol Siritanaratkul, Suthat Fucharoen, Prapon Wilairat, Jisnuson Svasti
  07/2009; 26(1):77-81.
• Article: DOUBLE HETEROZYGOSITY FOR Hb PYRGOS [β83(EF7)Gly→Asp] AND Hb E [β26(B8)Glu→Lys] FOUND IN ASSOCIATION WITH α-THALASSEMIA

  Phannee Sawangareetrakul, Saovaros Svasti, Boonpa Yodsowon, Pranee Winichagoon, Chantragan Srisomsap, Jisnuson Svasti, Suthat Fucharoen
  07/2009; 26(2):191-196.
• Source

  Available from: Jisnuson Svasti

  Article: Identification of HB Lepore-Mashington-Boston in Association with HB E [βB26(B8)GLU→LYS] in a Thai Female

  Pratumtip Boontrakoonpoontawee, Jisnuson Svasti, Suthat Fucharoen, Pranee Winichagoon
  [show abstract] [hide abstract]
  ABSTRACT: The proposita was a Thai female showing signs of a mild anemia (Hb: 11.4 g/dl; RBC: 4.91 × 106/mm3; reticulocytes: 2.4%; MCV: 70 fl; MCHC: 23.3 g/dl). Hemoglobins were isolated by DEAE-cellulose chromatography in the following relative amounts: Hb E + Hb A2 = 53%; Hb F0 = 30.0%; Hb δβ-Lepore = 12.7%; Hb F1 = 4.3%. The βE and δβ-Lepore chains were isolated by CM-cellulose chromatography and were subjected to tryptic peptide mapping on paper in comparison to normal βA chains. Amino acid analysis of selected peptides permitted unambiguous identification of the abnormal hemoglobins as Hb E [β26(B8)GluLys] and Hb Lepore-Washington-Boston, which has a δ chain sequence for residues 1-87, and a β chain sequence for residues 116-146. The presence of a Lepore hemoglobin was further confirmed by Pst I digestion of the proposita's DNA. The association of the two hemoglobin variants gave rise to elevated levels of Hb F.
  07/2009; 11(4):309-316.