Molecular defects in the β-globin gene identified in different ethnic groups/populations during prenatal diagnosis for β-thalassemia: a Malaysian experience

Abstract

Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.

A holistic approach to education programs in thalassemia for a multi-ethnic population: consideration of perspectives, attitudes, and perceived needs

“…In the case where patient cannot afford to pay for prenatal diagnosis, the service is given free and the cost is absorbed by the University. Thus, a decision with regards to the pregnancy can be made in the 12th week of gestation, with is within the first trimester of pregnancy (Tan et al 2004).…”

Specific and straightforward molecular investigation of β-thalassemia mutations in the Malaysian Malays and Chinese using direct TaqMan genotyping assays

“…DNA was extracted by a simplified DNA extraction method based on the protocol as reported previously (Tan et al, 2004). The concentration of DNA was determined using a nanophotometer.…”

“…Fortunately, thalassemia is caused by only a handful of specific mutations in each different ethnic group or population. However, molecular characterization of thalassemia in Malaysia is challenging because of the presence of various β-globin gene mutations in this multi-racial population (Tan et al, 2004). In addition, the Malaysian indigenous populations possess their own set of specific mutations (Tan et al, 2010).…”

“…In addition to these thalassemia mutations, HbE (G→A bp substitution at CD26) is the most common hemoglobin variant in the Malays (George and Ann, 2010). The common β-thalassemia mutations in the Malaysian Chinese are CD41/42 (-CTTT), IVS2-654 (C-T), -28 (A-G), CD17 (A-T), and CD71/72 (+A) (Tan et al, 2004).…”

Interaction of Hb South Florida (codon 1; GTG→ATG) and HbE, with β-thalassemia (IVS1-1; G→A): expression of different clinical phenotypes

“…DNA was extracted from the blood samples. Sixteen mutations in the β-globin [22]. The primer sequences to detect the β-globin mutations were paired with common ARMS primers to amplify each β-mutation as a specific molecular weight product.…”