3 PREVALENT MUTATIONS IN A PATIENT WITH PHENYLALANINE-HYDROXYLASE DEFICIENCY - IMPLICATIONS FOR DIAGNOSIS AND GENETIC-COUNSELING

Mutation analysis in a patient with mild hyperphenylalaninaemia showed three distinct base substitutions in exon 12 of the phenylalanine hyd roxylase (PAH) gene. All three mutations, R413P, Y414C, and D415N, hav e previously been described as being independently associated with PAH deficiency. Family studies and independent analysis of the PAH allele s of the patient showed cosegregation of the R413P and Y414C mutations . Data on the ethnic background of the family provide evidence that th e R413P mutation has occurred on a PAH allele carrying the Y414C mutat ion. Using current methods for mutation identification, the presence o f two known mutations on a single PAH allele implies the risk of misdi agnosis of PAH deficiency and complicates genetic counselling. Our res ults stress the need for comprehensive mutation scanning of the PAH ge ne in diagnostic settings.