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 μU/g hemoglobin [Hb] in erythrocyte PTPS activity (wild-type control: 11-29 μU/gHb) erythrocyte PTPS activity, and the patient with P87S/D96N mutations (52%/10%) had 0.97 μU/gHb in PTPS erythrocyte activity. The PTPS erythrocyte activity did not coincide with the in-vitro PTPS activity based on patient genotype.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Additional information
Received: October 27, 1998 / Accepted: December 15, 1998
Rights and permissions
About this article
Cite this article
Imamura, T., Okano, Y., Shintaku, H. et al. Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients. J Hum Genet 44, 163–168 (1999). https://doi.org/10.1007/s100380050134
Published:
Issue Date:
DOI: https://doi.org/10.1007/s100380050134
This article is cited by
-
In silico analysis and the pathogenicity classification of PTS gene variants among Iranian population
Egyptian Journal of Medical Human Genetics (2022)
-
Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations
Journal of Human Genetics (2012)
-
Commentary on the mutation spectrum of and founder effects affecting the PTS gene in East-Asian populations
Journal of Human Genetics (2012)
-
Novel mutation affecting the pterin‐binding site of PTS gene and review of PTS mutations in Thai patients with 6‐pyruvoyltetrahydropterin synthase deficiency
Journal of Inherited Metabolic Disease (2009)
-
Listening to silence and understanding nonsense: exonic mutations that affect splicing
Nature Reviews Genetics (2002)