Molecular characterization of QDPR gene in Iranian families with BH4 deficiency: Reporting novel and recurrent mutations

Abstract

Newborn screening for PKU has been in practice in Iran since 2007. Some hyperphenylalaninemia cases have tetrahydrobiopterin (BH4) biosynthesis deficiency/disorder. Several genes including QDPR (encodes DHPR enzyme, the necessary cofactor for PAH activity) have been associated with the BH4. Mutations have been previously described in the QDPR gene. The incidence of BH4 deficiency is expected to be higher in Iran due to high rate of consanguineous marriages. We identified a total of 93 BH4-deficient families. A multiplex set of STR markers linked to 4 genes responsible for the BH4 deficiency (i.e., GCH1, PCBD1, PTS, and QDPR genes) was used to quickly determine which gene may be responsible to cause the disease. Mutation analysis of QDPR gene revealed some known and novel mutations. Our findings show that no common mutation predominates, and they are scattered in the gene in our population.