AI Article Synopsis
- Pyruvate kinase (PK) deficiency is a genetic disorder marked by chronic hemolytic anemia and is caused by mutations in the PKLR gene.
- Researchers studied nine Polish patients with severe anemia who had normal PK activity and discovered both known and a new mutation (c.178C > T) in the PKLR gene.
- They further analyzed two specific mutations (c.1058delAAG and c.101-1G > A), concluding that one negatively affects PK's stability and function, while the other creates a defective mRNA that leads to a severely reduced PK protein.
Article Abstract
Pyruvate kinase (PK) deficiency is a rare autosomal recessive disorder characterized by chronic hemolytic anemia of variable severity. Nine Polish patients with severe hemolytic anemia but normal PK activity were found to carry mutations in the PKLR gene encoding PK, five already known ones and one novel (c.178C > T). We characterized two of the known variants by molecular modeling (c.1058delAAG) and minigene splicing analysis (c.101-1G > A). The former gives a partially destabilized PK tetramer, likely of suboptimal activity, and the c.101-1G > A variant gives alternatively spliced mRNA carrying a premature stop codon, encoding a severely truncated PK and likely undergoing nonsense-mediated decay.
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| http://dx.doi.org/10.1016/j.bcmd.2024.102841 | DOI Listing |
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