Molecular basis of Hb H and AEBart’s diseases in the Lao People’s Democratic Republic

Abstract

IntroductionAs compared to other neighboring countries, limited information on α‐thalassemia diseases is available for Lao PDR. We reported for the first time a genetic diversity associated with Hb H and AEBart's diseases in Laos patients.MethodsStudy was done on Laos patients with Hb H disease (n = 14) and AEBart's disease (n = 14) whose blood specimens were transferred to our laboratory for the investigation of thalassemia. Hematological parameters were recorded. Hb analysis was done using a capillary electrophoresis system. α‐ and β‐globin genotypes were determined using PCR and related techniques.ResultsHb and DNA analyses identified Hb H disease resulted from [‐‐SEA/−α3.7, βA/βA] (n = 7), [‐‐THAI/−α3.7, βA/βA] (n = 1), Hb H‐Constant Spring (CS) disease (‐‐SEA/αCSα, βA/βA; n = 5), and Hb H‐IVSI‐117 (‐‐SEA/ααIVSI‐117G>A, βA/βA; n = 1). For those of the AEBart's disease (n = 14), five were found to be AEBart's‐CS disease [‐‐SEA/αCSα, βE/βA], two had [‐‐THAI/αCSα, βE/βA] genotype, six had AEBart's disease with (‐‐SEA/−α3.7, βE/βA) genotype, and the remaining one was a patient with AEBart's‐Pakse′ [‐‐SEA/αPSα, βE/βA] disease. These ‐‐THAI and αIVSI‐117G>A mutations are reported herein for the first time in Laos population. Accurate diagnosis in most cases was obtained after DNA analysis.ConclusionsThis study demonstrates the diverse heterogeneity and highlights the importance of molecular diagnosis of α‐thalassemia diseases in Laos population. Data on the molecular basis of α‐thalassemia should prove useful for setting up a molecular diagnostic testing for thalassemia in Laos and further hemoglobin genetic study in the region.

β‐Hemoglobinopathies in the Lao People's Democratic Republic: Molecular diagnostics and implication for a prevention and control program

“…The remaining 287 (55.3%) subjects carried different β‐hemoglobinopathies. As the molecular basis of α‐thalassemia in Laotian patients has recently been reported, 6 we focused in this study on the 287 subjects with β‐hemoglobinopathies. As shown in Table 1, we identified several β‐hemoglobinopathies including Hb E carriers (n = 135), β‐thalassemia carriers (n = 70), homozygous Hb E (n = 47), Hb E‐β‐thalassemia (n = 25), homozygous β‐thalassemia (n = 4), δβ 0 ‐thalassemia carriers (n = 2), and carriers of the β‐Hb variant (n = 3).…”

“…Hemoglobinopathies are therefore major public health problems in this population. For α‐thalassemia, we have recently reported the molecular characteristic based on the study of Hb H and AEBart's diseases related to the interaction of α 0 ‐thalassemia and α + ‐thalassemia 6 . In contrast, the molecular data for β‐thalassemia have been limited to the Laos population.…”

“…As a result, cases with complex genotypes and phenotypes due to the interaction of these genes are commonly encountered during a routine investigation that needs an appropriate diagnostic approach. The molecular basis of α‐thalassemia in Lao PDR has recently been documented 6 . With regard to the molecular basis of β‐thalassemia, however, as compared to other Southeast Asian countries, limited information has been documented for Lao PDR.…”

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

“…To provide a method for rapid identification of the α Hb Amsterdam A1 , and α Hb Queens Park mutations found in this study, the PCR–RFLP assay using Bts CI restriction enzyme was developed. This method has been described for detection of the α IVSI-117(G>A) mutation (HBA1:c96-1G>A) located in the vicinity of the two variants on α1-globin gene [ 6 , 17 ]. Selective amplification of α1-globin specific fragment (975 bp) was performed by PCR using primers C1 (5′-GCCTCTTTGCACCATTCTAA-3′) and B (5′-AATGCACTGACCTCCCACAT-3′).…”

“…Most of the α + -thalassemia caused by the deletion of one α-globin gene (-α/αα) is generally mild [ 1 , 2 ]. Interaction of these α-thalassemia leads to the Hb H disease, and interaction of Hb H disease with Hb E leads to complex syndromes of AEBart’s, EFBart’s, and EEBart’s diseases, with thalassemia intermedia phenotypes, commonly encountered in the region [ 3 – 6 ]. However, the interaction of α 0 -thalassemia with non-deletional α + -thalassemia and some forms of homozygous α + -thalassemia caused by point mutations may result in more severe clinical phenotype and unstable Hbs, requiring appropriate management, treatment, and genetic counseling [ 7 – 9 ].…”