Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene

• Published in: Journal of medical genetics Vol. 34; no. 6; pp. 489 - 492
• Main Authors: von Schnakenburg, C, Rumsby, G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.1997; BMJ; BMJ Publishing Group LTD
• Subjects: Alanine Transaminase - genetics; Alleles; Base Sequence; Biological and medical sciences; Chromosomes, Human, Pair 2 - genetics; DNA Mutational Analysis; DNA Primers - genetics; Exons; Genes, Recessive; Humans; Hyperoxaluria, Primary - classification; Hyperoxaluria, Primary - enzymology; Hyperoxaluria, Primary - genetics; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Mutation; Other metabolic disorders; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Transaminases; Human; Genetic inheritance; Enzyme; Alanine-glyoxylate transaminase; Oxalate; Transferases; Metabolic diseases; Enzymopathy; Single strand conformation polymorphism; Genetic disease; Primitive; Transaminases; Genetics; Hyperoxaluria; Mutation
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.34.6.489

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single strand conformation polymorphism analysis to detect sequence variants, which were then characterised by direct sequencing and confirmed by restriction enzyme digestion. Four novel mutations were identified in exon 7 of AGXT: a point mutation T853C, which leads to a predicted Ile244Thr amino acid substitution, occurred in nine patients. Two other mutations in adjacent nucleotides, C819T and G820A, mutated the same codon at residue 233 from arginine to cysteine and histidine, respectively. The fourth mutation, G860A, introduced a stop codon at amino acid residue 246. Enzyme studies in these patients showed that AGT catalytic activity was either very low or absent and that little or no immunoreactive protein was present. Together with a new polymorphism in exon 11 (C1342A) these findings underline the genetic heterogeneity of the AGXT gene. The novel mutation T853C is the second most common mutation found to date with an allelic frequency of 9% and will therefore be of clinical importance for the diagnosis of PH1.