Identification of new mutations in two phosphoglycerate kinase (PGK)
variants expressing different clinical syndromes: PGK Creteil and PGK
Amiens
M Cohen-Solal, C Valentin, F Plassa, G Guillemin, F Danze, F Jaisson and R Rosa
Unite INSERM U91, Hopital Henri Mondor, Creteil, France.
Phosphoglycerate kinase (PGK) deficiency is generally associated with
chronic hemolytic anemia, although it can be accompanied by either mental
retardation or muscular disease. Genomic DNAs of two PGK- deficient
patients previously described in France were sequenced directly after
polymerase chain reaction amplification. The PGK Creteil variant arises
from a G-->A nucleotide interchange at position 1022 in cDNA (exon 9),
resulting in amino acid substitution 314 Asp-->Asn in the C-terminal
domain, which contains the nucleotide binding site. It is associated with
rhabdomyolysis crises but not with hemolysis or mental retardation. In the
other case, which is associated with chronic hemolytic anemia and mental
retardation (PGK Amiens), an A-->T nucleotide interchange was found at
position 571 in cDNA (exon 5); this leads to amino acid substitution 163
Asp-->Val in the N-terminal domain, which contains the catalytic site
for phosphoglycerate binding. These results corroborate the kinetic data
observed. In the two cases, the mutations are distinct from others
previously reported and no significant relationship could be observed
between the location of the amino acid substitution and its clinical
consequences.
Volume 84,
Issue 3,
pp. 898-903,
08/01/1994
Copyright © 1994 by The American Society of Hematology
