Beta-thalassemia major caused by compound heterozygosity for +40 to +43(-AAAC), IVS-2-654 (C to T) and codon 41/42 (-TCTT) / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>The triple mutation of [+40 to +43(-AAAC)*CD41/42(-TCTT)/N] is a new genotype of beta-thalassemia in Chinese.</p>