This study describes the mutations at the phenylalanine hydroxylase (PAH) locus in patients with the diagnosis of classic PKU (n=18), hyperphenylalaninemia (HPA) variant (n=9) and benign persistent hyperphenylalaninemia (HPA) (n=13) who were identified by the Texas Newborn Screening Program. Blinded studies were done by sequencing of the 13 exons and exon-intron boundaries of the PAH gene in genomic DNA isolated from dry blood spots. Thirty-six different mutations, including 25 missense mutations, six splice mutations, three deletions and two nonsense mutations were detected in 75 of the 80 mutant alleles (94%). The prevalent mutations were R408W (19%), V388M and IVS10nt-11g->a (6% each), Y414C (5%) and H170D, A403V, T380M and IVS7nt1g->a (4% each). Two novel missense mutations were identified in exon 5 (H170D and N167S). There was genotype/phenotype correlation in 33/40 cases (83%). For this population, exons 12, 11, 7, 5 and 8, which carry 78% of the mutations, would have to be screened first. However, the other exons must be studied when either one or no mutations are found in the primary screening. Hum Mutat 17:523, 2001.
Copyright 2001 Wiley-Liss, Inc.