en 28706611 <p>Background: <em>Phenylalanine hydroxylase (PAH) </em>gene is the well-known causative gene for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500 reported mutations. Through this study, a novel mutation in the <em>PAH </em>gene in an Iranian pedigree with phenylketonuria was introduced.<br /> Methods: A consanguineous family with a 10-year old affected girl was referred for genetic analysis. Mutation screening of all exons and exon-intron boundaries was performed by Sanger sequencing, and mini haplotype analysis was carried out by genotyping of Short Tandem Repeat (STR) and Variable Number Tandem Repeat (VNTR) alleles.<br /> Results: Mutation analysis revealed a novel homozygous insertion of a single adenine nucleotide at position 335 in exon 3 of the PAH gene. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the change is interpreted as a pathogenic mutation which produces a premature termination signal (TAA) at codon 113 according to in silico assessments. The mini haplotype analysis showed that this mutation was linked to STR (15) &ndash;VNTR (3).<br /> Conclusion: In this study, a novel mutation was reported in a patient who had PKU symptoms without any previously reported mutations in the <em>PAH</em> gene (NM_000277.1: p.Asp112Glufs*2) that can be responsible for the classical PKU phenotype in the Iranian population. Detection of novel mutations indicates notable allelic heterogeneity of the PAH locus among this population.</p> Mutation, Phenylalanine hydroxylase, Phenylketonurias, Population 146 149 https://www.ajmb.org/En/Article.aspx?id=283 https://www.ajmb.org/PDF/En/FullText/283.pdf ElahehAlavinejadDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1143Seyede ZahraSajediDepartment of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran1144MasoumehRazipourDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1145MonaEntezamDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1146NedaMohajerDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1147AriaSetoodehDepartment of Pediatrics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1148SaeidTalebiDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran735MohammadKeramatipourDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran18