Two novel polyadenylation mutations leading to beta(+)-thalassemia.
In an ongoing effort to identify point mutations causing beta-thalassaemia, we have found two previously unreported mutations which are located in the Poly A site of the beta-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----AATGAA 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 beta(+)-thalassemia. The second type involved an AATAAA----AATAGA mutation and was found in one family from Malaysia. The propositus had the beta E mutation on the other chromosome, was originally diagnosed as mild Hb E-beta(+)-thalassaemia, and had Hb A and Hb E percentages which were nearly the same.
Jankovic
L
L
Macedonian Academy of Sciences and Arts, Research Center for New Technologies, Skopje, Yugoslavia.
Efremov
G D
GD
Petkov
G
G
Kattamis
C
C
George
E
E
Yang
K G
KG
Stoming
T A
TA
Huisman
T H
TH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011061:Poly A / Q000235:genetics*; D013789:Thalassemia / Q000235:genetics*
D011061:Poly A; D005914:Globins