title: Identification of a common novel mutation in Saudi patients with argininosuccinic aciduria.
abstract: We have identified a common novel mutation (Q354X) in the argininosuccinate lyase (ASL) gene in Saudi patients with argininosuccinic aciduria (ASAuria; McKusick 207900). The two index patients were siblings, had a neonatal onset of the disease and were diagnosed based on the clinical presentation and confirmed by analysis of their dried blood spots (DBS) by tandem mass spectrometry (MS/MS). The ASL gene was then analysed by direct sequencing. A further 28 patients with a confirmed diagnosis of ASAuria based on MS/MS of their DBS were tested by sequencing for the presence of the Q354X mutation. This mutation was found in 14 out of the 28 patients (50%) tested. Our work indicates that the Q354X allele is common, may account for 50% of the abnormal ASL genes in the Saudi population, and is likely to be associated with the neonatal form of the disease. We recommend that all patients diagnosed with ASAuria in Saudi Arabia or of Arab origin be tested for this mutation and for Q116X, which has been described previously. In addition, further analysis is needed to identify other underlying disease mutations for ASAuria in the Saudi population.
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital & Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia. moeen@kfshrc.edu.sa
authors.forename: M
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: S
authors.initials: S
authors.lastname: Alahmed
authors.forename: O
authors.initials: O
authors.lastname: Alsmadi
authors.forename: H
authors.initials: H
authors.lastname: Khalil
authors.forename: M S
authors.initials: MS
authors.lastname: Rashed
authors.forename: F
authors.initials: F
authors.lastname: Imtiaz
authors.forename: B F
authors.initials: BF
authors.lastname: Meyer
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D001123:Argininosuccinate Lyase / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D016678:Genome; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation; D015997:Neonatal Screening; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001123:Argininosuccinate Lyase