title: A de novo mutation in the AGXT gene causing primary hyperoxaluria type 1.
abstract: Primary hyperoxaluria type 1 is caused by mutations in the alanine-glyoxylate aminotransferase (AGXT) gene. In cases in which no mutation was identified, linkage analysis can be used to confirm or exclude the diagnosis in other siblings. We present a family in which a sibling of the index case predicted to have primary hyperoxaluria type 1 by means of linkage analysis failed to show hyperoxaluria during the following 7 years, putting the diagnosis into question. Whole-gene sequence analysis identified 2 causative mutations in the index case, of which only 1, c.646A (Gly216Arg), was inherited. The other sequence change, c.33_34insC, was a de novo mutation occurring on the paternal allele. This particular mutation is a relatively common cause of primary hyperoxaluria type 1. It occurs in a run of 8 cytosines and therefore potentially is susceptible to polymerase slippage. This case illustrates 2 important points. First, biochemical confirmation of a genetic diagnosis should always be made in siblings diagnosed by using genetic tests. Second, de novo mutations should be considered as a potential, albeit rare, cause of primary hyperoxaluria type 1.
authors.affiliation: Clinical Biochemistry, UCL Hospitals, London, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Williams
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Kemper
authors.forename: Gill
authors.initials: G
authors.lastname: Rumsby
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D040582:Inheritance Patterns; D008297:Male; D009154:Mutation; D010375:Pedigree; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase