title: Identification of three novel missense PKU mutations among Chinese.
abstract: Three novel missense mutations have been identified in the phenylalanine hydroxylase (PAH) genes of Chinese individuals afflicted with various degrees of phenylketonuria (PKU). A T-to-C transition was observed in exon 5 of the gene, resulting in the substitution of Phe161 by Ser161. Two substitutions, G-to-T and T-to-G, were observed in exon 7, resulting in the substitution of Gly247 by Val247 and Leu255 by Val255, respectively. Expression analysis demonstrated that these mutant proteins produced between 0 and 15% of normal PAH enzyme activity. Population screening of a Chinese sample population indicates that these mutations are quite rare, together accounting for only about 4% of all PKU alleles among the Chinese. The P161S and G247V mutations were each present on a single PAH RFLP haplotype 4 chromosome in patients form Northern China, while the L255V mutation was present on chromosomes of both haplotypes 18 and 21 in patients from Southern China. These results suggest that the remaining 30% of uncharacterized PKU alleles in the Chinese population may bear a large number of relatively rare PAH mutations.
authors.affiliation: Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R C
authors.initials: RC
authors.lastname: Eisensmith
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: W H
authors.initials: WH
authors.lastname: Lo
authors.forename: S Z
authors.initials: SZ
authors.lastname: Huang
authors.forename: Y T
authors.initials: YT
authors.lastname: Zeng
authors.forename: L F
authors.initials: LF
authors.lastname: Yuan
authors.forename: S R
authors.initials: SR
authors.lastname: Liu
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000201:enzymology / Q000235:genetics*
chemical_list: D003062:Codon; D010651:Phenylalanine Hydroxylase