[Genetic diagnosis of phenylketonuria. III. Mutations of phenylalanine hydroxylase gene in Orientals].
Phenylketonuria (PKU) is an autosomal recessive disorder caused by lesions in the phenylalanine hydroxylase (PAH) gene. The recent studies on PAH mutations show the genetic drift of PKU alleles among some Oriental populations. Therefore, we searched for PKU mutations among Japanese, Chinese and Taiwanese. Direct sequencing was conducted on DNA fragments amplified by the polymerase chain reaction, using solid-phase technology involving the biotin-streptavidin system. Two new mutations (R241C and G247V) and two of the known mutant alleles (Y204C and R243Q) were found in two Taiwanese and two Chinese PKU patients, and three known mutations (R111X, Y204C and R413P) were recognized in three Japanese; two new mutations were identified in exon 7 of the PAH gene at codon 241 and codon 247, where the single base changes from C to T and from G to T substituted cysteine for arginine and valine for glycine, respectively. Further all the PAH mutations detected are common in Oriental populations as they have been thus far unreported among Caucasians. From these data as well as the clinical phenotype of the patients, we suggest that the R241C and G247V substitutions may interfere with proper enzyme function, although we have not yet performed functional studies. More detailed studies would be needed to clarify the regional distribution of mutant chromosomes in Oriental populations and other unidentified mutations.
Takarada
Y
Y
Clinical Laboratory, Hyogo College of Medicine, Nishinomiya.
Yamashita
K
K
Kagawa
S
S
Zhang
Q Z
QZ
Matsuoka
A
A
D000483:Alleles; D001208:Asia; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017421:Sequence Analysis
D010651:Phenylalanine Hydroxylase