title: Novel mutations of the AGXT gene causing primary hyperoxaluria type 1.
abstract: BACKGROUND
  Primary hyperoxaluria type 1 (PH1), an inherited cause of nephrolithiasis, is due to a functional defect of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). A definitive PH1 diagnosis can be established by analyzing AGT activity in liver tissue or mutation analysis of the AGXT gene.
  
  
  METHODS
  The molecular basis of PH1 in three Chinese patients, two with adult-onset and one with childhood-onset recurrent nephrolithiasis, was established by analyzing the entire AGXT gene.
  
  
  RESULTS
  Three novel mutations (c2T>C, c817insAG and c844C>T) and two previously reported mutations (c33insC and 679-IVS6+2delAAgt) were identified. c2T>C converts the initiation codon from ATG to ACG, which predicts significant reduction, if not complete abolition, of protein translation. c817insAG leads to a frameshift and changes the amino acid sequence after codon 274. c844C>T changes glutamine at codon 282 to a termination codon, resulting in protein truncation.
  
  
  CONCLUSIONS
  This is the first report describing AGXT gene mutations in Chinese patients with PH1. AGXT genotypes cannot fully explain the clinical heterogeneity of PH1, and other factors involved in disease pathogenesis remain to be identified. Our experience emphasizes the importance of excluding PH1 in patients with recurrent nephrolithiasis to avoid delay or inappropriate management.
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Yuet-Ping
authors.initials: YP
authors.lastname: Yuen
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Lai
authors.forename: Gensy Mei-Wah
authors.initials: GM
authors.lastname: Tong
authors.forename: Ping-Nam
authors.initials: PN
authors.lastname: Wong
authors.forename: Francis Kim-Ming
authors.initials: FK
authors.lastname: Wong
authors.forename: Siu-Ka
authors.initials: SK
authors.lastname: Mak
authors.forename: Kin-Yee
authors.initials: KY
authors.lastname: Lo
authors.forename: Andrew Kui-Man
authors.initials: AK
authors.lastname: Wong
authors.forename: Sui-Fan
authors.initials: SF
authors.lastname: Tong
authors.forename: Yan-Wo
authors.initials: YW
authors.lastname: Chan
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
mesh_terms: D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D006959:Hyperoxaluria / Q000235:genetics*; D007669:Kidney Calculi / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase