Rapid detection of deletions causing delta beta thalassemia and hereditary
persistence of fetal hemoglobin by enzymatic amplification
JE Craig, RA Barnetson, J Prior, JL Raven and SL Thein
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington,
Oxford, UK.
A considerable number of deletions of variable size and position that
involve the beta-globin gene complex on chromosome 11 are associated with
the clinical entities of hereditary persistence of fetal hemoglobin (HPFH)
and delta beta thalassemia. Specific deletions appear to be associated with
consistent phenotypes and some are known to be recurrent. To facilitate the
molecular diagnosis of uncharacterized patients with HPFH and delta beta
thalassemia, oligonucleotide primers have been designed to enzymatically
amplify deletion-specific products for nine known deletions, which include
those responsible for HPFH-1, HPFH-2, HPFH-3, Spanish (delta beta)zero
thalassemia, hemoglobin (Hb) Lepore, Sicilian (delta beta)zero thalassemia,
Chinese G gamma(A gamma delta beta)zero thalassemia, Asian-Indian
inversion-deletion G gamma(A gamma delta beta)zero thalassemia, and Turkish
inversion-deletion (delta beta)zero thalassemia. Using this approach, we
have successfully characterized the molecular basis for delta beta
thalassemia in 23 individuals from 16 families of diverse ethnic origins.
Thirteen individuals from this group were shown to be heterozygous for the
13.4- kb Sicilian deletion, two were heterozygous for the 100-kb Chinese G
gamma(A gamma delta beta)zero deletion, four were heterozygous for the
Turkish form of inversion-deletion delta beta thalassemia, and three were
heterozygous for the Asian-Indian form of inversion-deletion G gamma(A
gamma delta beta)zero thalassemia. One Vietnamese subject was heterozygous
for a 12.6-kb deletion, which we have fully characterized at the molecular
level. Sequence analysis of the breakpoint regions of the Chinese deletion
and the Turkish rearrangement indicates that, in each case, the mutation is
likely to have arisen from a single origin. This hypothesis is supported by
the evident geographical clustering of the various deletions described
here.
Volume 83,
Issue 6,
pp. 1673-1682,
03/15/1994
Copyright © 1994 by The American Society of Hematology
