2 NOVEL POLYADENYLATION MUTATIONS LEADING TO BETA+-THALASSEMIA

In an ongoing effort to identify point mutations causing β‐thalassaemia, we have found two previously unreported mutations which are located in the Poly A site of the β‐globin gene. The screening programme used amplified DNA and dot‐blot hybridization with several 32P‐labelled oligonucleotide probes. DNA samples which remained unidentified by this methodology were subjected to sequencing with 32P‐labelled primers and modified T7 DNA polymerase. The newly discovered mutations were confirmed by the dot‐blot hybridization technique. One type concerned an AATAAA→ÁTGAA mutation in the polyadenylation site and was found in one family from Yugoslavia (including one patient with the C→T mutation at codon 29 in trans), one from Bulgaria (the patient had the G→A mutation at IVS‐I‐110 in trans), and one from Greece (this patient had the C→G mutation at IVS‐II‐745 in trans). Haematological data for three simple heterozygotes suggested a rather mild β+‐thalassaemia. The second type involved an AATAAA→ÁTAGA mutation and was found in one family from Malaysia. The propositus had the βE mutation on the other chromosome, was originally diagnosed as mild Hb E‐β+‐thalassaemia, and had Hb A and Hb E percentages which were nearly the same. Copyright © 1990, Wiley Blackwell. All rights reserved