RNA transcripts of the beta-thalassaemia allele IVS-2-654 C-->T: a small amount of normally processed beta-globin mRNA is still produced from the mutant gene.
IVS-2-654 C-->T is a common Chinese beta-thalassaemia mutation. Previous studies report that this mutation resulted in the formation of an abnormally spliced mRNA and the absence of detectable normal beta-globin mRNA, hence the mutation was considered to cause beta o-thalassaemia. We recently used the method of PCR amplified cDNA copies of circulating erythroid cell mRNA to analyse the mutant gene transcripts and found that this IVS-2-654 mutation does not abolish normal RNA processing entirely, but that a significant amount (over 15%) of normally processed beta-globin mRNA is produced. Microglobin chain biosynthetic analysis using the HPLC method showed that beta-globin chain was also present in the blood of patients with IVS-2-654 C-->T mutation. Accordingly, this mutant allele leads to a beta (+)-thalassaemia. Further, the methodology described in this paper provides a new approach towards the detection of RNA transcripts of beta-thalassaemia alleles as well as the study of gene expression in beta-thalassaemia and other genetic diseases.
Huang
S Z
SZ
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, China.
Zeng
F Y
FY
Ren
Z R
ZR
Lu
Z H
ZH
Rodgers
G P
GP
Schechter
A N
AN
Zeng
Y T
YT
D000483:Alleles; D001483:Base Sequence; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000502:physiology; D015870:Gene Expression; D005914:Globins / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D017086:beta-Thalassemia / Q000235:genetics*
D012333:RNA, Messenger; D005914:Globins