PMID- 10369256
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20171116
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Jun
TI  - Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by
      mutations in a gene encoding a mitochondrial ornithine transporter.
PG  - 151-8
AB  - Neurospora crassa ARG13 and Saccharomyces cerevisiae ARG11 encode mitochondrial
      carrier family (MCF) proteins that transport ornithine across the mitochondrial
      inner membrane. We used their sequences to identify EST candidates that partially
      encode orthologous mammalian transporters. We thereby identified such a gene
      (ORNT1) that maps to 13q14 and whose expression, similar to that of other urea
      cycle (UC) components, was high in liver and varied with changes in dietary
      protein. ORNT1 expression restores ornithine metabolism in fibroblasts from
      patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH)
      syndrome. In a survey of 11 HHH probands, we identified 3 ORNT1 mutant alleles
      that account for 21 of 22 possible mutant ORNT1 genes in our patients: F188delta,
      which is common in French-Canadian HHH patients and encodes an unstable protein; 
      E180K, which encodes a stable, properly targeted protein that is inactive; and a 
      13q14 microdeletion. Our results show that ORNT1 encodes the mitochondrial
      ornithine transporter involved in UC function and is defective in HHH syndrome.
FAU - Camacho, J A
AU  - Camacho JA
AD  - Institute for Genetic Medicine, Johns Hopkins University School of Medicine,
      Baltimore, Maryland, USA.
FAU - Obie, C
AU  - Obie C
FAU - Biery, B
AU  - Biery B
FAU - Goodman, B K
AU  - Goodman BK
FAU - Hu, C A
AU  - Hu CA
FAU - Almashanu, S
AU  - Almashanu S
FAU - Steel, G
AU  - Steel G
FAU - Casey, R
AU  - Casey R
FAU - Lambert, M
AU  - Lambert M
FAU - Mitchell, G A
AU  - Mitchell GA
FAU - Valle, D
AU  - Valle D
LA  - eng
SI  - GENBANK/AF112968
SI  - GENBANK/AF133914
GR  - EY07414/EY/NEI NIH HHS/United States
GR  - GM07471/GM/NIGMS NIH HHS/United States
GR  - HD24061/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Amino Acid Transport Systems, Basic)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (SLC25A2 protein, human)
RN  - 0 (Slc25a15 protein, mouse)
RN  - 0 (ornithine transporter)
RN  - 29VT07BGDA (Citrulline)
RN  - 7664-41-7 (Ammonia)
RN  - E524N2IXA3 (Ornithine)
SB  - IM
MH  - Amino Acid Metabolism, Inborn Errors/*genetics
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Amino Acid Transport Systems, Basic
MH  - Ammonia/*blood
MH  - Animals
MH  - Canada
MH  - Carrier Proteins/biosynthesis/chemistry/*genetics
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 13
MH  - Citrulline/*metabolism
MH  - Female
MH  - France/ethnology
MH  - Genetic Carrier Screening
MH  - Humans
MH  - Karyotyping
MH  - Male
MH  - *Membrane Transport Proteins
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Molecular Sequence Data
MH  - Neurospora crassa/genetics
MH  - Ornithine/*blood/metabolism
MH  - Point Mutation
MH  - Saccharomyces cerevisiae/genetics
MH  - Sequence Alignment
MH  - Sequence Deletion
MH  - Sequence Homology, Amino Acid
MH  - Skin/metabolism
MH  - Syndrome
MH  - Transfection
EDAT- 1999/06/16 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/16 10:00
PHST- 1999/06/16 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/16 10:00 [entrez]
AID - 10.1038/9658 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jun;22(2):151-8. doi: 10.1038/9658.