Faculty Research 1990 - 1999
In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus.
Document Type
Article
Publication Date
1992
Keywords
Amino-Acid-Sequence, Animal, Base-Sequence, Cell-Line, Codon: ge, Exons, Female, France: eh, Genotype, Human, Isoleucine, Male, Molecular-Sequence-Data, Mutation, Oligodeoxyribonucleotides, Pedigree, Phenotype, Phenylalanine: me, Phenylalanine-Hydroxylase: ge, Polymerase-Chain-Reaction: mt, Quebec, SUPPORT-NON-U-S-GOVT, Threonine, Transfection
First Page
147
Last Page
153
JAX Source
Hum Mutat 1992;1(2):147-53
Abstract
Mutations at the phenylalanine hydroxylase (PAH) locus are the major cause of hyperphenylalaninemia. We have previously described four mutations (M1V, IVS12nt1, R408W, and S349P) at the PAH locus in French Canadians with ancestry in eastern Quebec. Here we report (1) identification of another mutation, on a haplotype 9 chromosome, which converts codon 65 from isoleucine (ATT) to threonine (ACT), (2) expression analysis of the I65T mutation in COS cells demonstrating 75% loss of both immunoreactive protein and enzyme activity, and (3) expression analysis of the most prevalent PKU allele (M1V) in eastern Quebec, showing nondetectable levels of PAH protein and activity, a finding compatible with a mutation in the translation initiation codon. Homozygosity for M1V and codominant inheritance of I65T/R408W were both associated with classical phenylketonuria.
Recommended Citation
John SW,
Scriver CR,
Laframboise R,
Rozen R.
In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. Hum Mutat 1992;1(2):147-53