Exp Mol Med.
2008 Oct;40(5):533-540. 10.3858/emm.2008.40.5.533.
Mutation analysis of PAH gene and characterization of a recurrent deletion mutation in Korean patients with phenylketonuria
- Affiliations
-
- 1Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang Univerisity College of Medicine, Bucheon, Korea.
- 2Department of Pediatrics, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
- 3Department of Laboratory Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
- 4R&D Center, Equispharm Co., Ltd, Suwon, Korea.
- 5Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. changski@skku.edu
- 6Department of Laboratory Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang Univerisity College of Medicine, Gumi, Korea.
- KMID: 1104807
- DOI: http://doi.org/10.3858/emm.2008.40.5.533
Abstract
- Phenylketonuria (PKU; MIM 261600) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase (PAH; EC 1.14.16.1). Point mutations in the PAH gene are known to cause PKU in various ethnic groups, and large deletions or duplications account for up to 3% of the PAH mutations in some ethnic groups. However, a previous study could not identify ~14% of the mutant alleles by sequence analysis in Korean patients with PKU, which suggests that large deletions or duplication might be frequent causes of PKU in Koreans. To test this hypothesis, we performed multiplex ligation-dependent probe amplification (MLPA) for the identification of uncharacterized mutant alleles after PAH sequence analysis of 33 unrelated Korean patients with PKU. Bi-directional sequencing of the PAH exons and flanking intronic regions revealed 27 different mutations, including four novel mutations (two missense and two deletion mutations), comprising 57/66 (86%) mutant alleles. MLPA identified a large deletion that encompassed exons 5 and 6 in four patients, another large deletion that extended from exon 4 to exon 7 in one patient, and a duplication of exon 4 in one patient. Chromosomal walking characterized the deletion breakpoint of the most common large deletion that involved exons 5 and 6 (c.456_706+138del). The present study shows that the allelic frequency of exon deletion or duplication is 9% (6/66) in Korean PKU patients, which suggests that these mutations may be frequent causes of PKU in Korean subjects.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- The Study of DNA Mutations of Phenylketonuria in Koreans
- Novel Point Mutation of EBSS Gene Coexisted with 1p36 Deletion
- The Analysis of Methylenetetrahydrofolate Reductase Mutation in Recurrent Spontaneous Abortion Associated with Hyperhomocysteinemia
- A case of familial X-linked thrombocytopenia with a novel WAS gene mutation
- Protein substitutions as new-generation pharmanutrition approach to managing phenylketonuria
