J Genet Med.  2008 Jun;5(1):26-33.

The Study of DNA Mutations of Phenylketonuria in Koreans

  • 1Department of Pediatrics, College of Medicine, Soonchunhyang University, Seoul, Korea. ldh@hosp.sch.ac.kr
  • 2Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital and College of Medicine, Soonchunhyang University, Buchoen, Korea.
  • 3Department of Biochemistry, College of Medicine, Ewha University, Seoul, Korea.
  • 4Department of Laboratory Medicine and Genetics, Samsung Medical Center, College of Medicine, Sungkyunkwan University, Seoul, Korea.


Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations.
DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA).
We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of BH4 responsive patients were analyzed and were divided into two groups: BH4 medication-only group and BH4 medication with diet therapy group. In the BH4 medication-only group and BH4 medication with diet therapy group, R241C was the most common mutation.
Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.


Phenylalanine hydroxylase; Phenylketonuria; Mutation; Tetrahydrobiopterin responsive PKU
Full Text Links
  • JGM
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr