Hg. Eiken et al., PHENYLKETONURIA GENOTYPES CORRELATED TO METABOLIC PHENOTYPE GROUPS INNORWAY, European journal of pediatrics, 155(7), 1996, pp. 554-560
In order to establish a genotype-phenotype relationship, we have ident
ified both mutant phenylalanine hydroxylase (PAH) genes in 108 phenylk
etonuria (PKU) patients (27 different alleles, 54 different genotypes)
. One major group of patients with very high pretreatment phenylalanin
e values (''classical'' PKU) exclusively comprised homozygotes of the
PKU mutations I65T, G272X, F299C, Y356X, R408W, IVS 12ntl, and compoun
d heterozygotes of various combinations of these alleles with G46S, R2
61Q, R252W, A259T, R158Q, D143G, R243X, E280 K, or Y204C. A second maj
or group of patients with lower phenylalanine values (''mild'' PKU) co
mprised mutations A300S, R408Q, Y414C in various compound heterozygous
states, and R261Q, R408Q, Y414C in homozygotes. The phenylalanine val
ues in these groups were non-overlapping. In addition, a smaller group
of patients formed the transition between the two main groups. In sib
pairs 4 of 15 had discordant pretreatment phenylalanine values. Concl
usion Our results are consistent with the view that allelic heterogene
ity at the PAH locus dominates the biochemical phenotype in PKU and th
at genotype information is able to predict the metabolic phenotype in
PKU patients.