Background: Neonatal screening for PKU is carried out nationally and our center is one of the referral centers for molecular analysis of PKU in Iran. Hyperphenylalaninemias are common disorders of phenyalanine catabolism. Six genes, including PAH, PTPS, DHPR, GTPCH, SR, and PCBD, independently play a role in this disorder.
Methods: A 2-year-old boy was referred to our center for genetic diagnosis of PKU. PAH gene was sequenced but no mutation was found. Using the STR based linkage mapping approach, BH4-metabolizing genes were screened.
Result: A pattern of autozygosity by descent (ABD) suggested that the PCBD gene may be involved in this family. The PCBD gene was sequenced and a homozygous T > C substitution (X105Q) was found in the termination codon.
Conclusion: Although most of the reported mutations in PCBD gene are single substitutions or premature stop codons causing a benign or transient form of BH4 deficiency, this novel mutation was found in the stop codon.