The polyadenylation site mutation in the alpha-globin gene cluster
SL Thein, RB Wallace, L Pressley, JB Clegg, DJ Weatherall and DR Higgs
Nuffield Department of Clinical Medicine, University of Oxford, John
Radcliffe Hospital, Headington, England.
In a previous study, we described a form of nondeletion alpha- thalassemia
(alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the
current study, using synthetic oligoprobe hybridization and restriction
enzyme analysis, we have demonstrated that the molecular basis of alpha T
Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in
the polyadenylation signal of the alpha 2 gene and that the frameshift
mutation in codon 14 of the linked alpha 1 gene is the result of a cloning
artefact. The alpha 2 polyadenylation signal mutation occurs in other
Middle Eastern and the Mediterranean populations and is responsible for the
clinical phenotype of Hb H disease in some Saudi Arabian individuals with
five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence
suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a
result of a recombination between two misaligned chromosomes bearing the
alpha T Saudi alpha defect.
Volume 71,
Issue 2,
pp. 313-319,
02/01/1988
Copyright © 1988 by The American Society of Hematology
