Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene

Human Mutation
Ljubica CaldovicMendel Tuchman

Abstract

N-acetylglutamate synthase (NAGS) deficiency, an autosomal recessive disorder, is the last urea cycle disorder for which molecular testing became available. This is the first comprehensive report of 21 mutations that cause NAGS deficiency and of commonly found polymorphisms in the NAGS gene. Five mutations are reported here for the first time. A total of 10 disease-causing mutations are associated with acute neonatal hyperammonemia; the remaining mutations were found in patients with late onset disease. Residual enzymatic activities are included in this report and the deleterious effects of eight mutations were confirmed by expression studies. Mutations in the NAGS gene are distributed throughout its reading frame. No mutations have been found in exon 1, which encodes for the putative mitochondrial targeting signal and variable segment of NAGS. Three polymorphisms have been found. Early, accurate, and specific diagnosis of NAGS deficiency is critical since this condition can be successfully treated with N-carbamylglutamate (NCG, Carbaglu; Orphan Europe). Treatment with NCG should be initiated as soon as a patient is suspected of having NAGS deficiency. Molecular testing represents the most reliable method of diagnosis.

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Citations

Mar 16, 2011·International Journal of General Medicine·Marta DaniottiLuca Filippi
Dec 20, 2012·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·A CartagenaC Prasad
Mar 23, 2010·Molecular Genetics and Metabolism·Ljubica CaldovicMendel Tuchman
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Jul 16, 2011·Biochimica Et Biophysica Acta·Barbara RengaStefano Fiorucci
Dec 25, 2012·Biochemical and Biophysical Research Communications·Gengxiang ZhaoDashuang Shi
May 1, 2012·Expert Review of Endocrinology & Metabolism·Johannes Häberle
Oct 12, 2019·Journal of Inherited Metabolic Disease·Lynne RumpingNanda M Verhoeven-Duif
Jan 24, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Gengxiang ZhaoDashuang Shi
Apr 16, 2019·Journal of Inherited Metabolic Disease·Johannes HäberleCarlo Dionisi-Vici
Jan 1, 2016·Expert Review of Endocrinology & Metabolism·Cristel C Chapel-CrespoKimihiko Oishi
Oct 11, 2020·Orphanet Journal of Rare Diseases·Aileen Kenneson, Rani H Singh

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