Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients

J Hum Genet. 1999;44(3):163-8. doi: 10.1007/s100380050134.

Abstract

We identified three mutations in four Japanese patients with central type 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. One missense mutation was a C-to-T transition, resulting in the substitution of Pro by Ser at codon 87 (P87S) in exon 5. Another missense mutation was a G-to-A transition, resulting in the substitution of Asp by Asn at codon 96 (D96N) in exon 5. A splicing mutation was found by skipping of exon 4 on PTPS mRNA analysis, and a G-to-A transition at the third base of codon 81 (E81E) and at the terminal base in exon 4 were detected on genomic PTPS DNA analysis. The E81E mutation affected the splice donor site of exon 4 and caused the splicing error. In COS cell expression analysis, the P87S and D96N mutant constructs revealed, respectively, 52% and 10% of wild-type activity. Patients with P87S/P87S (52%/52% in-vitro PTPS activity) exhibited 0.11 and 0 microU/g hemoglobin [Hb] in erythrocyte PTPS activity (wild-type control: 11-29 microU/gHb) erythrocyte PTPS activity, and the patient with P87S/D96N mutations (52%/10%) had 0.97 microU/gHb in PTPS erythrocyte activity. The PTPS erythrocyte activity did not coincide with the in-vitro PTPS activity based on patient genotype.

Publication types

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

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Asian People / genetics*
  • DNA, Complementary / genetics
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Japan
  • Male
  • Mutation, Missense*
  • Phenylalanine / blood
  • Phosphorus-Oxygen Lyases / deficiency*
  • Phosphorus-Oxygen Lyases / genetics*
  • Sequence Analysis, DNA

Substances

  • DNA, Complementary
  • Phenylalanine
  • Phosphorus-Oxygen Lyases
  • 6-pyruvoyltetrahydropterin synthase