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Introduction: A high frequency of β‐thalassemia in Lao People's Democratic Republic necessitates the importance of complete molecular data before a prevention and control program could be established. Limited data are available for Lao PDR. We have now reported an extended information on the molecular basis of β‐hemoglobinopathies in this population. Methods: The study was done on 519 unrelated Laos subjects requested for thalassemia investigation. Hematological data were recorded. Hb profiles were obtained using a capillary electrophoresis system. α‐And β‐globin genotyping was performed using PCR and related techniques. Results: Among the 519 subjects, 287 (55.3%) were found to carry β‐hemoglobinopathies based on Hb and DNA analyses. These included Hb E carriers (n = 135), homozygous Hb E (n = 47), β‐thalassemia carriers (n = 70), Hb E‐β‐thalassemia (n = 25), homozygous β‐thalassemia (n = 4), heterozygous δβ0‐thalassemia (n = 2), and carriers of the β‐Hb variant (n = 3). Mutation analysis identified in addition to the Hb E, 8 different β‐thalassemia mutations including codon 17 (A‐T), codons 41/42 (‐TTCT), NT‐28 (A‐G), codons 71/72 (+A), IVS1‐1 (G‐T), 3.4 kb deletion, an initiation codon (T‐G) and IVS2‐654 (C‐T). Two δβ0‐thalassemia carriers (12.6 kb deletion) and three subjects with Hb Hope (β136GGT‐GAT) were identified. Hematological features associated with these β‐hemoglobinopathies were presented. Conclusion: β‐hemoglobinopathies in the Laos population is heterogeneous. This information is relevant for setting up a molecular diagnostics and can provide a basis for genetic counseling and enable prenatal diagnosis. [ABSTRACT FROM AUTHOR]

The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and −154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), −154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and −154 (C-T) mutations. Significant higher Hb A level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome. [ABSTRACT FROM AUTHOR]

We report the molecular and hematological characteristics associated with a large cohort of β + -thalassemia in Thailand. Study was done on 21,068 unrelated subjects referred to our center in northeast Thailand for hemoglobinopathies investigation. Among 21,068 subjects, 2637 (12.5%) were found to carry β-thalassemia. Of these 2637 cases, 705 (26.7%) carried β + -thalassemia with eight different mutations including 6 promoter mutations; NT-28 (A–G), NT-31 (A–G), NT-50 (G–A), NT-86 (C–G), NT-87 (C–A) and NT-90 (C–T) and two missense mutations; Hb Malay (codon 19; A A C-A G C) and Hb Dhonburi (codon 126; G T G-G G G). Hematological features of carriers with these β + -thalassemia (n = 528) were compared with those with β 0 -thalassemia (n = 309). Data for Hb E-β + -thalassemia (n = 177) were also presented along with Hb E-β 0 -thalassemia in our series (n = 94). All patients with Hb E-β + -thalassemia were associated with mild thalassemia intermedia phenotypes. Most of the β + -thalassemia carriers had elevated Hb A 2 and mild hypochromic microcytosis, some demonstrated borderline MCV and MCH values which, could compromise carrier screening. Analysis of α/β-globin mRNA ratio in representative cases with normal, Hb E trait, β + -thalassemia trait, Hb Dhonburi trait and β 0 -thalassemia trait demonstrated the average values of 1.1, 1.7, 2.1, 1.7 and 3.1, respectively which is helpful in identification and differentiation of the cases. [ABSTRACT FROM AUTHOR]

Unlabelled: The cross-sectional study assessed anemia, thalassemia, and hemoglobinopathies, as well as iron deficiency, among 190 northeastern Thai school children aged 10 to 11 years. The aim was to analyze the reasons for anemia among the group. Hemoglobin concentration and other hematological parameters were determined using an automated blood cell counter. Beta-thalassemia and other hemoglobinopathies were identified by high performance liquid chromatography (HPLC) analysis of hemoglobin. Alpha-thalassemia was identified by polymerase chain reaction (PCR) and related techniques. Iron deficiency was assessed using serum ferritin (SF) <20 ng/ml as indicator. Based on the WHO criteria, anemia was defined by hemoglobin (Hb) level <11.5 g/dl. Twenty five out of 190 children (13.2%; 95% CI = 8.7-18.8%) were anemic. Iron deficiency was found in only two out of 190 children (1.0%; 95% CI = 0.1-3.8%), but the two iron deficient children were not anemic. The proportion of thalassemia and hemoglobinopathies among the group was 61.1% (95% CI = 53.7-68.0%). As underlying reasons for anemia, thalassemia and hemoglobinopathies were found in 22 out of 25 (88.0%) anemic children. Beta-thalassemia and homozygous Hb E seem to be important, while this was less obvious for heterozygous α-thalassemia and heterozygous Hb E.Conclusion: The results suggest that thalassemia and hemoglobinopathies may be major contributing factors to the occurrence of anemia in this area among the children's population. [ABSTRACT FROM AUTHOR]

We determined the prevalence of the H63D and the IVS5#1G-A HFE mutations in 370 (169 males and 201 females) Thai thalassemia carriers and 201 normal subjects. While no IVS5#1G-A mutation was found, the H63D heterozygosity was identified in 5.5% (11/201) of normal subjects and 7.3% (27/370) of thalassemia carriers. Within the thalassemic group, the medians (ranges) of serum ferritin were 217.5 ng/ml (20.1–424.3) and 169.8 ng/ml (3.9–3,536.0) in male subjects and 30.4 ng/ml (11.9–130.7) and 49.3 ng/ml (0.6–931.0) in female subjects with (HD) and without (HH) H63D mutation, respectively. The proportions of subjects with elevated ferritin were found to be 37.5% (6/16) for HD and 14.0% (18/129) for HH in male and 0% (0/11) for HD and 3.0% (5/164) for HH in female subjects, respectively. Statistical analysis of all the data revealed no significant difference. Among 14 Hb E/β-thalassemia patients, no difference in hematological data as well as serum ferritin levels was observed between those with (HD) and without (HH) H63D mutation. Therefore, the H63D heterozygosity has no significant effect on the serum ferritin level and screening for this HFE mutation in thalassemic patients is not recommended. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Study on the phenotypic expression of hemoglobin (Hb) A2 and Hb E in Hb E disorders has been difficult due to the co-separation of Hb A2 and Hb E in most Hb analysis assays. Because these two Hbs are separated on capillary electrophoresis, we studied phenotypic expression of Hbs A2, E and F in various Hb E disorders using this system. This was done on 362 subjects with several Hb E disorders including heterozygous Hb E, homozygous Hb E, β-thalassemia/Hb E, δβ-thalassemia/Hb E, and Hb Lepore/Hb E and those of these disorders with several forms of α-thalassemia. Normal controls showed Hb A2 of 2.7±0.3%. Heterozygous Hb E and homozygous Hb E had elevated Hb A2 i.e. 3.8±0.3% and 4.8±0.5%, respectively. Further elevations were observed for β0-thalassemia/Hb E (6.1±1.9%) and β+-thalassemia/Hb E (7.1±1.2%). Interestingly, no elevation of Hb A2 was found in the δβ-thalassemia/Hb E, and Hb Lepore/Hb E (2.3±0.3%) but higher Hb F levels were noted which could be useful diagnostic markers. The levels of Hb E were variable. Co-inheritance of these Hb E disorders with α-thalassemia were associated with lower outputs of Hb E and Hb F but the levels of Hb A2 were not altered. Different phenotypic expression of Hb A2, Hb E and Hb F could help in differential diagnosis of these Hb E related disorders commonly encountered in the regions where access to molecular techniques is limited. [Copyright &y& Elsevier]