Splice-site and Frameshift Mutations of β-Globin Gene Found in  Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

Handayani, Niken Satuti Nur; Husna, Nailil; Rahmil, Gunawan; Ghifari, Riris Anindya; Widyawati, Lily; Lesmana, Indra

doi:10.18585/inabj.v13i1.1406

Cited by 4 publications

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“…The results of our study are also comparable to a recent study reported in Yogyakarta Special Region, conducted on 28 patients which showed six (6) β-globin gene mutations with IVS-1-5 (G>C) being the most dominant (71.4%) (13).…”

Section: Discussionsupporting

confidence: 91%

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia

et al. 2022

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BackgroundThe frequency of the beta-thalassemia (β-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of β-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize β-thalassemia mutations in selected patients in the East Java province of Indonesia.MethodsThis is an analytical observational study. Diagnosis of β-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1–3 of the β-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing.ResultsIn total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 109/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with βCD26/βIVS−I−5; 6 (18.2%) with βCD26/βCD35; 3 (9.1%) with βCD26/βIVS−I−2; 2 (6.1%) with βCD27/28/βCD40; 2 (6.1%) with βIVS−I−1/βCAP+1; and βCD26/βIVS−I−1; βIVS−I−5/βCAP+1; βIVS−I−5/βCD35; βCD26/βCD37; βCD26/βCD15; βCD26/βCD40; and βIVS−I−5/βCD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The βCD26/βIVS−I−5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis.ConclusionThe underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was βCD26/βIVS−I−5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

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Section: Discussionsupporting

confidence: 91%

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia

et al. 2022

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“…(3) β-thalassemia is defined as a quantitative defect in production of β-globin chains due to mutation on β-globin (HBB) gene. (4,5) In attempt to simplify mass screening procedure, several indices using blood cell count parameters have been introduced to discriminate microcytic anemia due to β-thalassemia carrier (BTC) or iron deficiency (6) since iron deficiency anemia (IDA) is also common in Indonesia (7).…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte Indices MCV and/or MCH as First Round Screening Followed by Hb-analysis for β-thalassemia Carrier State

et al. 2022

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BACKGROUND: Being located in the global thalassemia belt area, Indonesia is estimated harboring about 10% thalassemia carriers; however, screening program is still diversely scattered across the country. Numerous erythrocyte indices have been introduced to help identifying thalassemia carriers with contradictory results. Therefore, this study had compared the use of mean corpuscular volume (MCV) and/or mean corpuscular hemoglobin (MCH) values and the most erythrocyte indices used in Indonesia which were Mentzer Index (MI) and Shine & Lal Index (SLI), as a first attempt in a mass screening for β-thalassemia carrier.METHODS: This was a retrospective study, evaluating laboratory data from family members of thalassemia major subjects. The sensitivity and specificity of MI and SLI were calculated. HbA2 >3.5% was used as a golden standard for β-thalassemia carrier and DNA examination was conducted to confirm β-globin mutation.RESULTS: Out of 160, 28.8% of the subjects had low Hb concentration. Interestingly, 79.4% of the subjects had low MCV and/or MCH with or without low Hb concentration. In this study, specificity and sensitivity of MI were 82.2% and 83.8%, whereas of SLI were 96% and 40.5%, respectively. Low MCV and/or MCH had covered IVS1nt5 and Cd26 mutation at β-globin gene; whereas MI and SLI had missed some samples, leading to false negative of thalassemia carrier results, when using MI or SLI only.CONCLUSION: MCV<80 fl and/or MCH<27 pg is the best first round mass screening method for β-thalassemia carrier in a limited facility area. However, Hb electrophoresis should be gradually installed regionally in various places wherever possible, as well as DNA analysis to confirm the mutation for an optimal carrier diagnosis.KEYWORDS: HbA2, HbE, iron deficiency anemia, Mentzer Index, Shine and Lal Index

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Mutation Spectrum of β-Globin Gene in Patients with β-Thalassemia at Tidar Hospital, Magelang, Central Java, Indonesia

‘Ulya,

Indrawati,

Wulansari

et al. 2023

Hemoglobin

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Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

Cited by 4 publications

References 17 publications

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia

Erythrocyte Indices MCV and/or MCH as First Round Screening Followed by Hb-analysis for β-thalassemia Carrier State

Mutation Spectrum of β-Globin Gene in Patients with β-Thalassemia at Tidar Hospital, Magelang, Central Java, Indonesia

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