Molecular basis of transfusion dependent beta-thalassemia major patients in Sabah

Abstract

Beta-thalassemia is one of the most prevalent inherited diseases and a public health problem in Malaysia. Malaysia is geographically divided into West and East Malaysia. In Sabah, a state in East Malaysia, there are over 1000 estimated cases of β-thalassemia major patients. Accurate population frequency data of the molecular basis of β-thalassemia major are needed for planning its control in the high-risk population of Sabah. Characterization of β-globin gene defects was done in 252 transfusion dependent β-thalassemia patients incorporating few PCR techniques. The study demonstrates that β-thalassemia mutations inherited are ethnically dependent. It is important to note that 86.9% of transfusion-dependent β-thalassemia major patients in Sabah were of the indigenous population and homozygous for a single mutation. The Filipino β(0)-deletion was a unique mutation found in the indigenous population of Sabah. Mutations common in West Malaysia were found in 11 (4.3%) patients. Four rare mutations (Hb Monroe, CD 8/9, CD 123/124/125 and IVS I-2) were also found. This study is informative on the population genetics of β-thalassemia major in Sabah.

Molecular Characterisation of α‐ and β‐Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia

“…IVS 1–5 (G>C) was found only in the Jah Hut subethnic group with an allelic frequency of 1.9%. Both IVS 1–5 (G>C) and Cd 26 (G>A) are the two most common β ‐thalassaemia alleles in the Malays in Malaysia and have been reported in the Javanese (Teh et al., ), Thai (Boonyawat et al., ; Thedsawad et al., ), Myanmar (Ne‐Win et al., ), Indian (Bohara et al., ; Colah et al., ) and Azerbaijan (Akbarova, ) populations.…”

Haplotype Analysis of β-Thalassaemia Major and Carriers with Filipino β°-Deletion in Sabah, Malaysia

“…The major ethnic groups are the Kadazandusun (25%), followed by the Bajau (15%), Murut (3%) and others. A high carrier rate of β-thalassaemia is reported in Sabah, with the Filipino β°-deletion as the predominant mutation (4).…”

“…The Filipino β°-deletion [NG_000007.3:g.66258_184734del118477] was first reported in a Filipino family (2). In later, Filipino β°-deletion was also found in 45.8% of the β-globin mutant alleles in Filipinos in Taiwan (3), 86.9% of transfusion dependent β-TM patients in Sabah (4), 16 out of 125 members of the Kadazandusun ethnic group (5), 19 out of 20 β-TM families (6) and 20 Dusun children from the indigenous communities in Sabah, East Malaysia (7).…”

“…The population of Sabah in East Malaysia is predominantly indigenous with their own distinct set of β-thalassaemia mutations (4). The Filipino β°-deletion has been reported as the predominant mutation in Sabah, East Malaysia (4).…”

“…The population of Sabah in East Malaysia is predominantly indigenous with their own distinct set of β-thalassaemia mutations (4). The Filipino β°-deletion has been reported as the predominant mutation in Sabah, East Malaysia (4). The haplotype pattern for the β-globin gene is informative in determining genetic diversity diversity in a specific population based on frequencies and number of haplotypes.…”