Molecular characterization of β‐globin gene mutations in Malay patients with Hb E‐β‐thalassaemia and thalassaemia major

K. G. Yang, Ferdane Kutlar, E. George, J. B. Wilson, Abdullah Kutlar, T. A. Stoming, J. M.Gonzalez Redondo, T. H.J. Huisman

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Abstract

Summary. This study concerned the identification of the β‐thalassaemia mutations that were present in 27 Malay patients with Hb E‐β‐thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all β‐thalassaemia chromosomes carried the G → C substitution at nucleotide 5 of IVS‐I; the commonly occurring Chinese anomalies such as the frameshift at codons 41 and 42, the nonsense mutation A → T at codon 17, the A → G substitution at position −28 of the promoter region, and the C → T substitution at position 654 of the second intron, were rare or absent. Two new thalassaemia mutations were discovered. The first involves a frameshift at codon 35 (‐C) that was found in two patients with Hb E‐β°‐thalassaemia and causes a β°‐thalassaemia because a stop codon is present at codon 60. The second is an AAC → AGC mutation in codon 19 that was present on six chromosomes. This substitution results in the production of an abnormal β chain (β‐Malay) that has an Asn → Ser substitution at position β19. Hb Malay is a‘Hb Knossos‐like’β+‐thalassaemia abnormality; the A → G mutation at codon 19 likely creates an alternate splicing site between codons 17 and 18, reducing the efficiency of the normal donor splice site at IVS‐I to about 60%.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalBritish Journal of Haematology
Volume72
Issue number1
DOIs
StatePublished - Jan 1 1989

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Globins
beta-Thalassemia
Codon
Thalassemia
Mutation
Genes
Chromosomes, Human, 21-22 and Y
RNA Splice Sites
Terminator Codon
Nonsense Codon
Malaysia
Alternative Splicing
Genetic Promoter Regions
Introns
Nucleotides
Chromosomes

ASJC Scopus subject areas

  • Hematology

Cite this

Molecular characterization of β‐globin gene mutations in Malay patients with Hb E‐β‐thalassaemia and thalassaemia major. / Yang, K. G.; Kutlar, Ferdane; George, E.; Wilson, J. B.; Kutlar, Abdullah; Stoming, T. A.; Redondo, J. M.Gonzalez; Huisman, T. H.J.

In: British Journal of Haematology, Vol. 72, No. 1, 01.01.1989, p. 73-80.

Research output: Contribution to journalArticle

Yang, K. G. ; Kutlar, Ferdane ; George, E. ; Wilson, J. B. ; Kutlar, Abdullah ; Stoming, T. A. ; Redondo, J. M.Gonzalez ; Huisman, T. H.J. / Molecular characterization of β‐globin gene mutations in Malay patients with Hb E‐β‐thalassaemia and thalassaemia major. In: British Journal of Haematology. 1989 ; Vol. 72, No. 1. pp. 73-80.
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AB - Summary. This study concerned the identification of the β‐thalassaemia mutations that were present in 27 Malay patients with Hb E‐β‐thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all β‐thalassaemia chromosomes carried the G → C substitution at nucleotide 5 of IVS‐I; the commonly occurring Chinese anomalies such as the frameshift at codons 41 and 42, the nonsense mutation A → T at codon 17, the A → G substitution at position −28 of the promoter region, and the C → T substitution at position 654 of the second intron, were rare or absent. Two new thalassaemia mutations were discovered. The first involves a frameshift at codon 35 (‐C) that was found in two patients with Hb E‐β°‐thalassaemia and causes a β°‐thalassaemia because a stop codon is present at codon 60. The second is an AAC → AGC mutation in codon 19 that was present on six chromosomes. This substitution results in the production of an abnormal β chain (β‐Malay) that has an Asn → Ser substitution at position β19. Hb Malay is a‘Hb Knossos‐like’β+‐thalassaemia abnormality; the A → G mutation at codon 19 likely creates an alternate splicing site between codons 17 and 18, reducing the efficiency of the normal donor splice site at IVS‐I to about 60%.

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