Tina Shirzad - Medical Genetics Lab, Kawsar Human Genetics Research Center, Tehran, Iran
Maziyeh Mojbafan - Medical Genetics Lab, Kawsar Human Genetics Research Center, Tehran, Iran
Hamideh Bagherian - Medical Genetics Lab, Kawsar Human Genetics Research Center, Tehran, Iran
Zohreh Sharifi - Medical Genetics Lab, Kawsar Human Genetics Research Center, Tehran, Iran

Hyperphenylalaninemia is a condition characterized by elevated level of phenylalanine in the blood which is results from deficiency in phenylalanine metabolic pathway. Any defects in the PAH gene that constructs Phenylalanine hydroxylase, as the main enzyme in Phenylalanine breaking down process, leads to phenylketonuria. Five other essential genes also contribute in these pathways which are called PTS, PCBD1, GCH1, SPR and QDPR can cause hyperphenylalanemia too. In the present study co-segregation of this disease was investigated by six sets of short tandem repeat (STR) markers linked to the PAH and other mentioned genes. Here we have ruled out PAH deficiency in 3 families based on the clinical and biochemical examinations. haplotype analysis of these families were performed using five multiplex sets of STR markers linked to genes responsible for BH4 deficiency such as GCH1, PCBD1, PTS, QDPR and SRP. Autozygosity mapping followed by Sanger sequencing has led us to the causative mutation. In silico analysis of the observed mutation was performed by on line softwares such as Polyphen-2, Hope project and mutation taster. Autozygosity mapping showed same haplotypes in affected members in the mentioned families. Sanger sequencing revealed a same missense mutation which is located in exon 5 in all affected members. According to the mentioned softwares, this mutation is a damaging one.The mutation was occurred in an almost conserved residue which can disturb protein function, therefore it can be concluded that the mutation is a disease causing one.Observing same mutation with same haplotype suggested a founder mutation in QDPR gene in Iranian patients. More sample size is needed to confirm our results.

Hyperphenylalaninemia, QDPR, autozygosity mapping,Iran