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

Patients with mitochondrial ornithine transporter deficiency (or HHH syndro me) present with various neurological symptoms, including mental retardatio n, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodi c disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients wit h 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). Furthermor e, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a pre viously reported patient with R179X. These results, together with the findi ngs in our previous report, show that, in three of our five reported Japane se HHH patients (six of ten alleles), R179X is present, suggesting that thi s is a common mutation in Japanese patients with HHH syndrome.