Mutation analysis in patients with N-acetylglutamate synthase deficiency

Human Mutation
J HäberleHans Georg Koch

Abstract

N-acetylglutamate synthase (NAGS) is the key enzyme for the regulation of the hepatic urea cycle and is also highly expressed in kidney and gut. The reaction product, N-acetylglutamate, is an allosteric activator of carbamylphosphate synthetase 1 in the liver, catalyzing the initial step of ammonia detoxification. NAGS deficiency is a rare inborn error of metabolism inherited as an autosomal recessive trait leading to hyperammonemia. Using homology search based on genetic information of ascomycetes, we identified the human gene for NAGS on chromosome 17q21.31. There is a distinct pattern of organospecific expression of transcripts in liver, small intestine, and kidney similar to the other mitochondrially located enzymes of the urea cycle. The encoded 534 amino acid polypeptide has a consensus sequence for a 49 amino acid mitochondrial leader peptide. We identified private mutations of the NAGS gene in patients with severe early onset of clinical symptoms (IVS3-2A>T, c.1306_1307insT, c.971G>A/W324X, c.1289T>C/L430P, c.1299G>C/E433S, c.1450T>C/W484R), as well as in a case with late onset (c.835G>A/A279P). Four out of seven mutations were detected on exon 6. This is the first report of mutation analysis in a series of families aff...Continue Reading

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Citations

Mar 31, 2004·Molecular Genetics and Metabolism·Hiroki MorizonoMendel Tuchman
Oct 13, 2009·The Journal of Clinical Endocrinology and Metabolism·Jefferson P LomenickJames W Anderson
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
Jun 13, 2015·International Journal of Molecular Sciences·Dashuang ShiMendel Tuchman
Aug 31, 2010·Molecular Genetics and Metabolism·Ana Isabel MartínezJavier Cervera
Mar 23, 2010·Molecular Genetics and Metabolism·Ljubica CaldovicMendel Tuchman
Oct 16, 2007·Molecular Genetics and Metabolism·Joshua L DeignanWayne W Grody
Apr 7, 2016·Scientifica·Swati ChaturvediSudipta Saha
Apr 11, 2007·Human Mutation·Ljubica CaldovicMendel Tuchman
Dec 3, 2005·Molecular Genetics and Metabolism·Ljubica CaldovicMendel Tuchman
Aug 30, 2005·The Journal of Pediatrics·Nathalie GuffonChristine Vianey-Saban
Jul 16, 2011·Biochimica Et Biophysica Acta·Barbara RengaStefano Fiorucci
Feb 26, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Carmen Diez-FernandezJohannes Häberle
Feb 17, 2005·Human Mutation·Ljubica CaldovicMendel Tuchman
May 1, 2012·Expert Review of Endocrinology & Metabolism·Johannes Häberle
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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