Details

Autor(en) / Beteiligte

• Wang, Tao
• Okano, Yoshiyuki
• Eisensmith, Randy C.
• Harvey, Michele L.
• Wilson H. Y. Lo
• Huang, Shu-Zhen
• Zeng, Yi-Tao
• Yuan, Li-Fang
• Furuyama, Jun-Ichi
• Oura, Toshiaki
• Sommer, Steve S.
• Savio L. C. Woo

Titel

Founder Effect of a Prevalent Phenylketonuria Mutation in the Oriental Population

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1991-03, Vol.88 (6), p.2146-2150

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1991

Quelle

MEDLINE

Beschreibungen/Notizen

• A missense mutation has been identified in the human phenylalanine hydroxylase [PAH; phenylalanine 4-monooxygenase; L-phenylalanine, tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1] gene in a Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro413for Arg413in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that "northern Mongoloids" represented a founding population in Asia. Our results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations.