Mutational analysis of AGXT in two Chinese families with primary hyperoxaluria type 1.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver -specific peroxisomal enzyme alanine :glyoxylate aminotransferase (AGT ) that leads to hyperoxaluria , recurrent urolithiasis , and nephrocalcinosis .Two unrelated patients with recurrent urolithiasis , along with members of their families , exhibited mutations in the AGXT gene by PCR direct sequencing .Two heterozygous mutations that predict truncated proteins , p .S 81 X and p .S 275 delinsRAfs , were identified in one patient . The p .S 81 X mutation is novel . Two heterozygous missense mutations , p .M 1 T and p .I 202 N , were detected in another patient but were not identified in her sibling . These four mutations were confirmed to be of paternal and maternal origin .These are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China . The novel p .S 81 X and p .I 202 N mutations detected in our study extend the spectrum of known AGXT gene mutations .