Identification of new mutations in two phosphoglycerate kinase (PGK) variants expressing different clinical syndromes: PGK Creteil and PGK Amiens

Abstract

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.

Two new phosphoglycerate kinase mutations associated with chronic haemolytic anaemia and neurological dysfunction in two patients from Spain

“…By reviewing previously described PGK mutations, it appears that the majority of the 14 single amino acid substitutions reported to date, occur in three specific regions of the enzyme molecule ( Fig 1A). The first region, located in the N-domain of PGK, incorporates the mutations PGK-Barcelona, PGK-Matsue and PGK-Amien (Cohen-Solal et al, 1994), representing the 21% of all PGK single amino acid substitutions. The second region is located in the C-domain and includes PGK-Murcia, PGK-Herlev, PGK-Michigan and PGK-Creteil, representing 28% of PGK amino acid substitutions.…”

Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis

“…S5B). Moreover, the biological function of PGK1 K323 acetylation in restoring cell proliferation still depends on its catalytic activity because additional D164V enzymatic dead mutation (29) completely abolished the effect of PGK1-K323Q (Supporting Fig. S5C,D).…”

Rare hereditary red blood cell enzymopathies associated with hemolytic anemia – pathophysiology, clinical aspects, and laboratory diagnosis

“…Thus, PGK deficiency shows a very wide clinical phenotype. Some cases of PGK deficiency with myopathy but without hemolysis have been described [30][31][32][33][34].…”