Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X

J Hum Genet. 2001;46(5):260-2. doi: 10.1007/s100380170075.


Patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Transport Systems, Basic
  • Carrier Proteins / genetics*
  • Child
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Female
  • Homozygote
  • Humans
  • Japan
  • Male
  • Membrane Transport Proteins*
  • Middle Aged
  • Mitochondria / chemistry*
  • Ornithine / blood
  • Point Mutation*
  • Syndrome


  • Amino Acid Transport Systems, Basic
  • Carrier Proteins
  • Codon, Nonsense
  • Membrane Transport Proteins
  • SLC25A2 protein, human
  • ornithine transporter
  • Ornithine