PMID- 10484776
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 11
DP  - 1999 Oct
TI  - The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with
      primary hyperoxaluria type II.
PG  - 2063-9
AB  - Primary hyperoxaluria type II (PH2) is a rare monogenic disorder that is
      characterized by a lack of the enzyme that catalyzes the reduction of
      hydroxypyruvate to D-glycerate, the reduction of glyoxylate to glycolate and the 
      oxidation of D-glycerate to hydroxypyruvate. The disease is characterized by an
      elevated urinary excretion of oxalate and L-glycerate. The increased oxalate
      excretion can cause nephrolithiasis and nephrocalci-nosis and can, in some cases,
      result in renal failure and systemic oxalate deposition. We identified a
      glyoxylate reductase/hydroxypyruvate reductase (GRHPR) cDNA clone from a human
      liver expressed sequence tag (EST) library. Nucleotide sequence analysis
      identified a 1198 nucleotide clone that encoded a 984 nucleotide open reading
      frame. The open reading frame encodes a predicted 328 amino acid protein with a
      mass of 35 563 Da. Transient transfection of the cDNA clone into COS cells
      verified that it encoded an enzyme with hydroxy-pyruvate reductase, glyoxylate
      reductase and D-glycerate dehydrogenase enzymatic activities. Database analysis
      of human ESTs reveals widespread tissue expression, indicating that the enzyme
      may have a previously unrecognized role in metabolism. The genomic structure of
      the human GRHPR gene was determined and contains nine exons and eight introns and
      spans approximately 9 kb pericentromeric on chromosome 9. Four PH2 patients
      representing two pairs of siblings from two unrelated families were analyzed for 
      mutations in GRHPR by single strand conformation polymorphism analysis. All four 
      patients were homozygous for a single nucleotide deletion at codon 35 in exon 2, 
      resulting in a premature stop codon at codon 45. The cDNA that we have identified
      represents the first characterization of an animal GRHPR sequence. The data we
      present will facilitate future genetic testing to confirm the clinical diagnosis 
      of PH2. These data will also facilitate heterozygote testing and prenatal testing
      in families affected with PH2 to aid in genetic counseling.
FAU - Cramer, S D
AU  - Cramer SD
AD  - Department of Cancer Biology, Wake Forest University School of Medicine,
      Winston-Salem, NC 27157, USA. scramer@wfubmc.edu
FAU - Ferree, P M
AU  - Ferree PM
FAU - Lin, K
AU  - Lin K
FAU - Milliner, D S
AU  - Milliner DS
FAU - Holmes, R P
AU  - Holmes RP
LA  - eng
SI  - GENBANK/AF146018
SI  - GENBANK/AF146689
SI  - GENBANK/AL031180
SI  - GENBANK/D31857
SI  - GENBANK/D49432
SI  - GENBANK/P37666
SI  - GENBANK/T72836
GR  - R01-DK54468-01/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Codon)
RN  - 0 (DNA, Complementary)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.81 (Hydroxypyruvate Reductase)
SB  - IM
EIN - Hum Mol Genet 1999 Dec;8(13):2574
MH  - Alcohol Oxidoreductases/deficiency/*genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Cercopithecus aethiops
MH  - Codon/genetics
MH  - Consensus Sequence
MH  - DNA, Complementary/genetics
MH  - Exons/genetics
MH  - Expressed Sequence Tags
MH  - Genes
MH  - Humans
MH  - Hydroxypyruvate Reductase
MH  - Hyperoxaluria/classification/enzymology/*genetics
MH  - Liver/chemistry
MH  - Molecular Sequence Data
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Species Specificity
MH  - Transfection
EDAT- 1999/09/15 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/09/15 09:00
PHST- 1999/09/15 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/09/15 09:00 [entrez]
AID - ddc231 [pii]
AID - 10.1093/hmg/8.11.2063 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Oct;8(11):2063-9. doi: 10.1093/hmg/8.11.2063.