Primary hyperoxaluria type 1: genotypic and phenotypic heterogeneity.

摘要: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT). The notable for its extensive heterogeneity at clinical, biochemical, enzymic and molecular genetic levels. A study 116 PH1 patients over past 8 years has revealed four main phenotypes: (1) absence both AGT catalytic activity immunoreactive protein (≈40% patients); (2) but presence (≈16% (3) (≈41% patients), in most which cases mistargeted to mitochondria instead peroxisomes; (4) variation mistargeting phenotype equally distributed between peroxisomes mitochondria, that aggregated into matrical core-like structures (≈3% patients). Various point mutations, all occurring conserved positions coding regions gene, have been identified these patients. five mutations discussed present study, found individuals manifesting major phenotypes, account expressed alleles about half Caucasian common mutation so far leads Gly170 → Arg amino acid substitution. This mutation, combination with normally Pro11 Leu polymorphism, appears be responsible unprecedented peroxisome-to-mitochondrion phenotype.