A double mutation in AGXT gene in families with primary hyperoxaluria type 1.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type 1 (PH 1 ) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2 q 37 .3 that encodes the hepatic peroxisomal enzyme alanine :glyoxylate aminotransferase . These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity . Rare in Europe , PH 1 is responsible for 13 % of the end stage renal failure in the Tunisian child . In the present work , we identified the double mutation c .32 C >T (Pro 11 Leu ) and c .731 T >C (p .Ile 244 Thr ) in AGXT gene in five unrelated Tunisian families with PH 1 disease . Our results provide evidence regarding the potential involvement of c .32 C >T , originally described as common polymorphism , on the resulting phenotype . We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH 1 . Despite the same genetic background , the outcome of the affected members differs widely . The significant phenotypic heterogeneity observed within a same family , with a same genotype , suggests the existence of relevant modifier factors .