Molecular study and genotype/phenotype correlation of β thalassemia in Malaysia

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Abstract

Introduction: To study the ß-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients. Methods: A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and ß gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR. Results: A total of 19 ß Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0%, 15.2%, and 89.2%, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort. Conclusion: Molecular analysis should be used for a better diagnosis and management of β thalassemia.

Original languageEnglish
Pages (from-to)377-382
Number of pages6
JournalInternational Journal of Laboratory Hematology
Volume34
Issue number4
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Thalassemia
Malaysia
Genetic Association Studies
Polymorphism
beta-Thalassemia
Genes
Mutation
Refractory materials
Amplification
Multiplex Polymerase Chain Reaction
DNA Sequence Analysis
Restriction Fragment Length Polymorphisms
DNA
Polymerase Chain Reaction
Population

Keywords

  • Alpha thalassemia
  • Beta mutations
  • Beta thalassemia
  • Molecular testing
  • Xmn-1 polymorphism

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Hematology

Cite this

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title = "Molecular study and genotype/phenotype correlation of β thalassemia in Malaysia",
abstract = "Introduction: To study the {\ss}-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients. Methods: A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and {\ss} gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR. Results: A total of 19 {\ss} Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0{\%}, 15.2{\%}, and 89.2{\%}, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort. Conclusion: Molecular analysis should be used for a better diagnosis and management of β thalassemia.",
keywords = "Alpha thalassemia, Beta mutations, Beta thalassemia, Molecular testing, Xmn-1 polymorphism",
author = "M. Sivalingam and Looi, {M. L.} and {Syed Zakaria}, {Syed Zulkifli} and Hussin, {Noor Hamidah} and Hamidah Alias and {Abdul Latiff}, Zarina and H. Ibrahim and {A. Jamal}, {A. Rahman}",
year = "2012",
month = "8",
doi = "10.1111/j.1751-553X.2012.01405.x",
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T1 - Molecular study and genotype/phenotype correlation of β thalassemia in Malaysia

AU - Sivalingam, M.

AU - Looi, M. L.

AU - Syed Zakaria, Syed Zulkifli

AU - Hussin, Noor Hamidah

AU - Alias, Hamidah

AU - Abdul Latiff, Zarina

AU - Ibrahim, H.

AU - A. Jamal, A. Rahman

PY - 2012/8

Y1 - 2012/8

N2 - Introduction: To study the ß-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients. Methods: A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and ß gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR. Results: A total of 19 ß Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0%, 15.2%, and 89.2%, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort. Conclusion: Molecular analysis should be used for a better diagnosis and management of β thalassemia.

AB - Introduction: To study the ß-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients. Methods: A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and ß gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR. Results: A total of 19 ß Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0%, 15.2%, and 89.2%, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort. Conclusion: Molecular analysis should be used for a better diagnosis and management of β thalassemia.

KW - Alpha thalassemia

KW - Beta mutations

KW - Beta thalassemia

KW - Molecular testing

KW - Xmn-1 polymorphism

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