title: Novel mutation in the GRHPR gene in a Chinese patient with primary hyperoxaluria type 2 requiring renal transplantation from a living related donor.
abstract: We identified a patient with primary hyperoxaluria type 2 (PH2) showing recurrent stone formation, nephrocalcinosis, end-stage renal failure, and rapid oxalate deposition after renal transplantation from a living related donor. Urinary organic acid analysis performed after renal transplantation confirmed the diagnosis of PH2. We analyzed the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene of the patient. DNA sequencing of all nine exons and exon-intron boundaries showed a novel homozygous mutation deleting the last two nucleotides of exon 8, ie, 862delTG. This deletion results in a frameshift and introduction of a premature stop codon at codon 310, ie, Ala310Stop. One of the patient's sisters is heterozygous for this mutation, and the other sister, who is the donor, does not have this mutation. The rapid deposition of oxalate in the transplanted kidney indicates that the kidney is not a major site of oxalate production. The more favorable long-term prognosis of PH2 needs to be reevaluated now that the molecular basis of PH2 has been established. DNA-based diagnosis will facilitate carrier detection, prenatal diagnosis, genetic counseling, and selection of living related donors.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. ching-wanlam@cuhk.edu.hk
authors.forename: C W
authors.initials: CW
authors.lastname: Lam
authors.forename: Y P
authors.initials: YP
authors.lastname: Yuen
authors.forename: C K
authors.initials: CK
authors.lastname: Lai
authors.forename: S F
authors.initials: SF
authors.lastname: Tong
authors.forename: L K
authors.initials: LK
authors.lastname: Lau
authors.forename: K L
authors.initials: KL
authors.lastname: Tong
authors.forename: Y W
authors.initials: YW
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D050537:Hydroxypyruvate Reductase; D006959:Hyperoxaluria / Q000235:genetics*; D007669:Kidney Calculi / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004247:DNA; D000429:Alcohol Oxidoreductases; C020830:glyoxylate reductase; D050537:Hydroxypyruvate Reductase