title: Mutation spectrum of phenylketonuria in Syrian population: genotype-phenotype correlation.
abstract: Characterization of the molecular basis of phenylketonuria (PKU) in Syria has been accomplished through the analysis of 78 unrelated chromosomes from 39 Syrian patients with PKU. Phenylalanine hydroxylase (PAH) gene mutations have been analyzed by using molecular detection methods based on the restriction fragment length polymorphism (RFLP), artificial constructed restriction sites (ACRS) PCR and direct DNA sequencing. 56.4% of the patients had cPKU. A mutation detection rate of 79.49% was achieved and sixteen different mutations were found: missense 56.25%, splice site 37.5%, and frameshift 6.25%. The predominant mutation in this population sample was p.R261Q G>A, p.F55>Lfs and p.R243Q G>A. No mutation in six PKU patients was observed. In 57.9% of patient genotypes, the metabolic phenotype could be predicted. The identification of the mutations in the PAH gene and the genotype-phenotype correlation should facilitate the evaluation of metabolic phenotypes, diagnosis, implementation of optimal dietary therapy, and determination of prognosis in the patients and genetic counseling for the patient's relatives.
authors.affiliation: Molecular Biology and Biotechnology Department, Human Genetics Division, Atomic Energy Commission, Damascus, Syria. ascientific@aec.org.sy
authors.forename: Hossam
authors.initials: H
authors.lastname: Murad
authors.forename: Amir
authors.initials: A
authors.lastname: Dabboul
authors.forename: Faten
authors.initials: F
authors.lastname: Moassas
authors.forename: Diana
authors.initials: D
authors.lastname: Alasmar
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Achkar
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D022821:RNA Splice Sites; D013593:Syria
chemical_list: D022821:RNA Splice Sites; D010651:Phenylalanine Hydroxylase
keywords: AV; Genotype; HPA; IVS; MHP; PAH; PKU; PRA; Phe; Phenotype; Phenylketonuria; Syria; arbitrary value; hyperphenylalaninemia; intervening sequences; mild hyperphenylalaninemia; phenylalanine; phenylalanine hydroxylase; phenylketonuria; predicted residual activity