Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency and a founder effect for the R241C mutation.
The spectrum of phenylalanine hydroxylase (PAH) gene mutations was determined in 25 families of hyperphenylalaninemia identified by a neonatal screening program in Taiwan. The coding sequence and exon-flanking intron sequences of PAH gene were amplified and sequenced. Mutations were identified in forty-five of the 50 chromosomes. R241C was the most common mutation (36% of the chromosomes), followed by R408Q (14% of the chromosomes). The remaining mutations were rare and seven mutations have not been reported before: p.F233L (c.697T>C), p.R252Q (c.756G>A), p.E286K (c.856G>A), p.G312V (c.935G>T), p.P314T (c.940C>A), p.I95del (c.284_286delTCA), and p.T81fsX6 (c.241_256del). Both p.R241C and p.R408Q are classified as mild phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) mutation, which may explain the fact that classical PKU is very rare in Taiwan (n=4, or one in 413,035). This strong founder effect for the p.R241C mutation has been described neither in the Caucasian populations, nor in other reports from Chinese. Since most of the populations in Taiwan are derived from Southeastern China, the spectrum of PAH gene mutations in Southeastern China should be different from other Chinese populations. This report not only disclose a specific spectrum of PAH gene mutation in Taiwan, but may also give clues to the movement of populations in Mainland China.
Chien
Yin-Hsiu
YH
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Chiang
Shu-Chuan
SC
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Huang
Aichu
A
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Chou
Shi-Ping
SP
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Tseng
Szu-San
SS
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Huang
Yuan-Te
YT
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hwu
Wuh-Liang
WL
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics; D001120:Arginine / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D018703:Founder Effect; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D020125:Mutation, Missense / Q000235:genetics*; D015997:Neonatal Screening; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000172:deficiency* / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis / Q000235:genetics; D013624:Taiwan
D001120:Arginine; D010651:Phenylalanine Hydroxylase; D003545:Cysteine