Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand

Abstract

Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-β-thalassemia, 1 with homozygous β⁰-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For β-thalassemia, 12 different mutations including both β⁰- and β⁺-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with β-thalassemia. The α-globin gene triplicated haplotype (ααα^anti3.7) was observed in 1 case of Hb E-β⁰-thalassemia. The presence of the -158 (C→T) ^Gγ-XmnI polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients.

MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-Β-Thalassemia DISEASE WITHOUT Α--Thalassemia

“…It has been known that co-inheritance of α-thalassemia is associated with a mild phenotype of the Hb E - β - thal disease. However, we have demonstrated previously that among Hb E - β 0 - thal patients associated with NTDT phenotypes, co-inheritance of α - thalassemia could explain the phenotypic expression only in a few cases 18. We report in this study, the existence of several genetic modifying SNPs in the HBS1L - MYB, BCL11A, and KLF1 genes among 122 clinically well - defined NTDT Hb E - β - thal patients in northeast Thailand.…”

Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia in Northeast Thailand

“…Diagnosis and awareness, as well as an understanding of the basis of NTDT, are therefore important [19,20,21]. Although most of β-thalassemia diseases are transfusion dependent, we recently noted that more than half of the NTDT patients encountered in Northeast Thailand are associated with Hb E-β-thalassemia [22]. To understand the basis of NTDT in β-thalassemia, we performed a molecular characterization of 73 adult Thai patients selectively recruited from those who were non-transfusion dependent and had a stably exhibited thalassemia intermedia phenotype with mild hypochromic microcytic anemia.…”

“…All of them were diagnosed as having β-thalassemia intermedia based on a complete blood count, an Hb analysis, and their transfusion history [6]. A total of 73 subjects including 28 males and 45 females were recruited.…”

“…However, it is difficult to predict the clinical phenotype of Hb E-β-thalassemia patients based on the type of β-thalassemia mutation alone [4,5]. A recent study of patients with non-transfusion-dependent thalassemia (NTDT) in Northeast Thailand revealed, unexpectedly, a high proportion of the β⁰-thalassemia mutation among Hb E-β-thalassemia diseases [6]. It is indicated that, in addition to the type of β-thalassemia mutation, other underlying genetic factors also play an important role in the clinical diversity of the disease [7,8].…”

Screening of (–SEA) α-thalassaemia using an immunochromatographic strip assay for the ζ-globin chain in a population with a high prevalence and heterogeneity of haemoglobinopathies

“…In Thailand and south-east Asian countries the prevalence of α-thalassaemia is reported to be 30–40% 2. While the homozygous state of α 0 -thalassaemia is associated with a fatal condition known as haemoglobin (Hb) Bart's hydrops fetalis syndrome, the compound heterozygote of α 0 - and α + -thalassaemias can lead to the Hb H disease with thalassaemia intermedia phenotype, commonly encountered in the region 3 4. Identification of α 0 -thalassaemia is therefore useful for genetic thalassaemia counselling.…”