Germline p53 single-base changes associated with Balkan endemic nephropathy.
The Balkan endemic nephropathy (BEN) is a significant clinical and scientific problem in need of novel effective therapies. Though many genetic and environmental factors have been investigated the basis, cause, and predisposition to BEN are still unclear. In this study, based on the hypothesis that the genetic pathways leading to BEN might be associated with p53 dysfunction, we screened for p53 gene mutations 90 Bulgarian BEN patients using optimized PCR-SSCP-sequencing analysis. Germline p53 single-base changes were found in blood samples in 10% of BEN cases. Three of them caused amino acid substitutions (p.Arg283Cys, p.Gln317His, and p.Lys321Glu); the other six were either synonymous amino acid substitutions (p.Arg213Arg) or intron polymorphisms (T14766C). To the best of our knowledge, these are the first data investigating tumor suppressor gene mutations in patients with BEN. The obtained results are in support of our hypothesis that p53 gene alterations are possibly involved in BEN genetic pathways.
Krasteva
Maria Emileva
ME
Institute of Genetics, Department of Molecular Genetics, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Georgieva
Elena Ivanova
EI
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001449:Balkan Nephropathy / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53