Inter-individual variation in brain phenylalanine concentration in patients with PKU is not caused by genetic variation in the 4F2hc/LAT1 complex.
It remains a question why some patients with phenylketonuria (PKU) have high IQ and low brain phenylalanine (Phe) concentrations in spite of high blood Phe levels. One possible explanation for the low brain Phe concentrations in these patients would be a reduced transport of Phe across the blood-brain barrier. The 4F2hc/LAT1 complex has been suggested to be the most important molecular component responsible for this transport. To test the hypothesis that structural variant(s) in the genes encoding 4F2hc and LAT1 might result in a complex with reduced affinity for Phe, we have screened the two genes for sequence variants in a group of 13 PKU patients with a low ratio of brain to blood Phe concentrations. Several common sequence variants were identified, but none of these is predicted to affect the resulting protein product. Our data suggest that individual vulnerability to Phe in patients with PKU is not due to structural variants in the 4F2hc/LAT1 complex.
Møller
Lisbeth Birk
LB
Kennedy Institute, Glostrup, Denmark. LBM@kennedy.dk
Paulsen
Marianne
M
Koch
Richard
R
Moats
Rex
R
Guldberg
Per
P
Güttler
Flemming
F
D000328:Adult; D001483:Base Sequence; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D005091:Exons; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007360:Intelligence; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010649:Phenylalanine / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D010661:Phenylketonurias / Q000097:blood / Q000235:genetics* / Q000473:pathology
D027282:Fusion Regulatory Protein 1, Heavy Chain; D027283:Large Neutral Amino Acid-Transporter 1; D010649:Phenylalanine