Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major.
This study concerned the identification of the beta-thalassaemia mutations that were present in 27 Malay patients with Hb E-beta-thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all beta-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-beta zero-thalassaemia and causes a beta zero-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 beta chain (beta-Malay) that has an Asn----Ser substitution at position beta 19. Hb Malay is a 'Hb Knossos-like' beta +-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%.
Yang
K G
KG
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Kutlar
F
F
George
E
E
Wilson
J B
JB
Kutlar
A
A
Stoming
T A
TA
Gonzalez-Redondo
J M
JM
Huisman
T H
TH
D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D005796:Genes; D005914:Globins / Q000235:genetics*; D006446:Hemoglobin E / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008296:Malaysia; D009154:Mutation; D013789:Thalassemia / Q000208:ethnology / Q000235:genetics*
D003062:Codon; D006455:Hemoglobins, Abnormal; D005914:Globins; D006446:Hemoglobin E