In a patient with mild phenylketonuria (PKU; 261600), Caillaud et al. (1991) reported a 3-bp in-frame deletion resulting in loss of isoleucine-94. The mutant enzyme showed markedly reduced affinity for phenylalanine. Since the deletion was located in the third exon of the gene, which shows no homology with other hydroxylases, Caillaud et al. (1991) suggested that exon 3 is involved in the specificity of PAH for phenylalanine. It appeared that this mutation may have occurred recently on the background of a haplotype II gene in Portugal.
In patients with PKU from the Old Order Amish in Lancaster County, Pennsylvania, Wang et al. (2007) identified compound heterozygosity for 2 PAH mutations: R261Q (612349.0006) and the 3-bp deletion at codon 94. The incidence of PKU in the Lancaster County Amish was 1 in 10,000, similar to that in other populations.
