A nationwide molecular characterization of β-thalassemia and variants among a referred trio families in Malaysia
Abstract
Thalassemia is a significant health burden in Malaysia. This report presents a retrospective analysis of nationwide diagnostic data compiled over seven years, investigating β-thalassemia spectrum in 731 referred family trios. Genomic analysis used gap-PCR, ARMS-PCR, MLPA, Sanger sequencing, and exome sequencing to validate rare CNVs. We identified 468 at-risk couples, with 440 children inherited biallelic mutations. Heterogeneous mutations were recorded among Peninsular Malaysian children with 43 β-, four δ-, 11 α-thalassemia and variant types, and five α-globin duplications. Among children in Sabah, 15 β-, one δ-, and two α-thalassemia and variants, and one α-globin duplications were recorded. Sarawak exhibited lowest heterogeneity. In Peninsular Malaysia, β E was most prevalent among Malays, followed by IVS 1–5 (G > C), β Malay , and IVS 1–1 (G > T). IVS 2–654 (C > T) and − 28 (A > G) were observed only among Chinese individuals in this referred cohort, while Cd 41/42 -TTCT was common to both ethnicities. β E /β-thalassemia was the most frequent disease with 188 cases. In Sabah, homozygous β Filipino was the most frequent genotype across multiple ethnicities, with 35.2% (31/88) of these cases exhibiting concomitant -α 3.7 . Overall, 15.2% (111/731) of children with HBB mutations had concomitant α-thalassemia, and 10 had α-triplications. These findings highlight the necessity of HBA genotyping for accurate genetic counseling. We present two novel mutation, codon 122 (TTC > TGC) mutation (HBB:c.368 T > G; p.Phe123Cys) named β Tanah Merah , and α-globin cluster duplication, ααα ⁹¹ (NC_000016.10:g.87820_179080dup). This comprehensive dataset is essential for improving molecular diagnostics and optimizing DNA analysis workflows in highly heterogeneous populations.
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BibTeX
@article{hassan2026nationwide,
title = {{A nationwide molecular characterization of β-thalassemia and variants among a referred trio families in Malaysia}},
author = {Syahzuwan Hassan and Zefarina Zulkafli and Yuslina Mat Yusoff and Rahimah Ahmad and Zubaidah Zakaria and Norafiza Mohd Yasin and Faidatul Syazlin Abdul Hamid and Nur Aisyah Aziz and Ermi Neiza Mohd Sahid and Azian Naila Md Nor and Suguna Somasundram and Siti Nurrazan Zulkifli and Nurul Hidayah Musa and Gowrisankari Navaretnam and Ulfatul Khusna Samuri and Sharifah Sarah Syed Mohamad Alwi and Ezzanie Suffya Zulkefli and Syahira Lazira Omar and Velintina Matnih and Mohd Khairul Nizam Mohd Khalid and Muhammad Farid Johan and Rosnah Bahar and Wan Zaidah Abdullah and Ezzeddin Kamil Mohamed Hashim and Ezalia Esa},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73362-5},
url = {https://www.nature.com/articles/s41598-026-73362-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A nationwide molecular characterization of β-thalassemia and variants among a referred trio families in Malaysia
AU - Syahzuwan Hassan
AU - Zefarina Zulkafli
AU - Yuslina Mat Yusoff
AU - Rahimah Ahmad
AU - Zubaidah Zakaria
AU - Norafiza Mohd Yasin
AU - Faidatul Syazlin Abdul Hamid
AU - Nur Aisyah Aziz
AU - Ermi Neiza Mohd Sahid
AU - Azian Naila Md Nor
AU - Suguna Somasundram
AU - Siti Nurrazan Zulkifli
AU - Nurul Hidayah Musa
AU - Gowrisankari Navaretnam
AU - Ulfatul Khusna Samuri
AU - Sharifah Sarah Syed Mohamad Alwi
AU - Ezzanie Suffya Zulkefli
AU - Syahira Lazira Omar
AU - Velintina Matnih
AU - Mohd Khairul Nizam Mohd Khalid
AU - Muhammad Farid Johan
AU - Rosnah Bahar
AU - Wan Zaidah Abdullah
AU - Ezzeddin Kamil Mohamed Hashim
AU - Ezalia Esa
PY - 2026
DA - 2026/10/04
JO - Scientific Reports
DO - 10.1038/s41598-026-73362-5
UR - https://www.nature.com/articles/s41598-026-73362-5
AB - Thalassemia is a significant health burden in Malaysia. This report presents a retrospective analysis of nationwide diagnostic data compiled over seven years, investigating β-thalassemia spectrum in 731 referred family trios. Genomic analysis used gap-PCR, ARMS-PCR, MLPA, Sanger sequencing, and exome sequencing to validate rare CNVs. We identified 468 at-risk couples, with 440 children inherited biallelic mutations. Heterogeneous mutations were recorded among Peninsular Malaysian children with 43 β-, four δ-, 11 α-thalassemia and variant types, and five α-globin duplications. Among children in Sabah, 15 β-, one δ-, and two α-thalassemia and variants, and one α-globin duplications were recorded. Sarawak exhibited lowest heterogeneity. In Peninsular Malaysia, β E was most prevalent among Malays, followed by IVS 1–5 (G > C), β Malay , and IVS 1–1 (G > T). IVS 2–654 (C > T) and − 28 (A > G) were observed only among Chinese individuals in this referred cohort, while Cd 41/42 -TTCT was common to both ethnicities. β E /β-thalassemia was the most frequent disease with 188 cases. In Sabah, homozygous β Filipino was the most frequent genotype across multiple ethnicities, with 35.2% (31/88) of these cases exhibiting concomitant -α 3.7 . Overall, 15.2% (111/731) of children with HBB mutations had concomitant α-thalassemia, and 10 had α-triplications. These findings highlight the necessity of HBA genotyping for accurate genetic counseling. We present two novel mutation, codon 122 (TTC > TGC) mutation (HBB:c.368 T > G; p.Phe123Cys) named β Tanah Merah , and α-globin cluster duplication, ααα ⁹¹ (NC_000016.10:g.87820_179080dup). This comprehensive dataset is essential for improving molecular diagnostics and optimizing DNA analysis workflows in highly heterogeneous populations.
SN - 2045-2322
ER -