[Beta-thalassemia major caused by compound heterozygosity for +40 to +43(-AAAC), IVS-2-654 (C to T) and codon 41/42 (-TCTT)].
OBJECTIVE
To report the analysis of a rare beta-thalassemia ternary heterozygote [+40 to +43(-AAAC)*CD41/42(-TTCT)*IVS-2-654] causing beta-thalassemia major in a Chinese.


METHODS
Using PCR-ASO probe hybridization analysis to scan 17 known types of beta-thalassemia mutations, and gene cloning and DNA sequencing to identify the underlying causative mutation.


RESULTS
Reverse dot blot (RDB) analysis showed that the patient's beta-globin gene had three mutations: +40 to +43(-AAAC), CD41/42(-TCTT) and IVS-2-654(C to T). Beta-globin gene cloning and sequencing proved that, the two deletions of +40 to +43(-AAAC) and CD41/42(-TCTT) co-existed on the same chromosome, and the other homologous chromosome had an IVS-2-654 (C to T) mutation. So the patient is a compound heterozygote of [+40 to +43(-AAAC)*CD41/42 (-TCTT)]/IVS-2-654 (C to T) leading to beta-thalassemia major.


CONCLUSIONS
The triple mutation of [+40 to +43(-AAAC)*CD41/42(-TCTT)/N] is a new genotype of beta-thalassemia in Chinese.
Hu
Zhao-hui
ZH
Guangzhou Kingmed Center for Clinical Laboratory, Guangzhou, Guangdong, 510330 People's Republic of China. zhaohuihu@yahoo.co
Liu
Yuan-li
YL
Zeng
Zheng-yu
ZY
Zhang
Xiao-lu
XL
Zhu
Qing-yi
QY
D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D017086:beta-Thalassemia / Q000235:genetics*
D003062:Codon