Concordance of a point mutation 5' to the G gamma globin gene with G gamma
beta +. Hereditary persistence of fetal hemoglobin in the black population
FS Collins, CD Boehm, PG Waber, CJ Stoeckert , SM Weissman, BG Forget and HH Kazazian
Hereditary persistence of fetal hemoglobin (HPFH) is a genetically
heterogeneous and clinically benign condition characterized by persistent
expression of fetal hemoglobin (Hb F) into adulthood. In the G gamma beta +
type, no major deletions in the globin gene cluster occur; adult
heterozygotes produce approximately 20% Hb F, which results from
overproduction of G gamma chains, with no apparent increase in production
from the adjacent A gamma gene. We have recently described a point mutation
202 base pairs 5' to the cap site of the G gamma gene in an individual with
G gamma beta + HPFH. This mutation abolishes a normal ApaI restriction
endonuclease site, and thus can be detected by blotting of genomic DNA. We
present here further data on the ApaI mutation: (1) It occurs in six of
seven families with G gamma beta + HPFH. (2) In three families, detailed
haplotype analysis using 11 polymorphic restriction sites in the beta
globin cluster has been done. The two that carry the missing ApaI site are
identical but the third, which has a normal ApaI pattern, differs from the
other two in at least two sites, one of which is a new polymorphic Nco I
site between the delta and beta globin genes. This suggests the possibility
of a different HPFH mutation in the third family. (3) The haplotype of the
G gamma beta + HPFH chromosome carrying the ApaI mutation is different from
that of 108 beta A chromosomes of black individuals that have been tested.
(4) The G gamma ApaI site is normal in 61 beta A and 109 beta S alleles
from non-HPFH black individuals, including 22 who share the same haplotype
for the intragenic G gamma, A gamma HindIII polymorphisms. These data add
support to the possibility that the -202 mutation is actually causative of
the G gamma beta + HPFH phenotype.
Volume 64,
Issue 6,
pp. 1292-1296,
12/01/1984
Copyright © 1984 by The American Society of Hematology
