PMID: 9163320Apr 15, 1997Paper

A nonsense mutation in the 3-hydroxy-3-methylglutaryl-CoA lyase gene produces exon skipping in two patients of different origin with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

The Biochemical Journal
Juan PiéF G Hegardt

Abstract

A novel nonsense mutation associated with the skipping of constitutive exon 2 of the 3-hydroxy-3-methylglutaryl-CoA lyase gene was found in two patients, from Portugal and Morocco, with 3-hydroxy-3-methylglutaric acidemia. By reverse transcriptase PCR and single-strand conformational polymorphism a G-T transversion was located, at nucleotide 109, of the 3-hydroxy-3-methylglutaryl-CoA lyase cDNA, within exon 2. Two mRNAs were produced as a result of this nonsense mutation: one of the expected size that contains the premature stop codon UAA, and the other with a deletion of 84 bp corresponding to the whole of exon 2. This deletion produced the loss of the last seven amino acids of the leader peptide and the first 21 amino acids of the mature protein. The nonsense mutation was found in a purine-rich GGAAG sequence, which is equal to, or similar to, others reported to be exonic splicing enhancers (ESE). We suggest that the nonsense mutation may affect a possible ESE on exon 2, which would hinder the splice site selection and facilitate an aberrant splice with the skipping of this exon. Determination by quantitative PCR shows that the ratio of mRNA with the nonsense mutation to the mRNA with the deletion is approx. 3:1.

Citations

May 29, 2004·Journal of Physiology and Biochemistry·J PieF G Hegardt
May 15, 2003·The Journal of Biological Chemistry·Núria CasalsFausto G Hegardt
Jan 18, 2006·Human Molecular Genetics·Raymonda VaronPaola Maraschio
Mar 5, 2017·Italian Journal of Pediatrics·Juan Ignacio Muñoz-BonetJosé Luis León Guijarro
Feb 16, 2020·Orphanet Journal of Rare Diseases·Sarah C Grünert, Jörn Oliver Sass
Dec 18, 2007·Journal of Inherited Metabolic Disease·C R VargasM Wajner
Dec 19, 2006·BMC Medical Genetics·Moeenaldeen Al-SayedBrian F Meyer
Oct 2, 2003·Journal of Inherited Metabolic Disease·E PospísilováJ Zeman
Jan 5, 2002·Journal of Inherited Metabolic Disease·H SugieI Nonaka
Nov 7, 1998·Mutation Research·C R Valentine
Apr 27, 2007·Molecular Genetics and Metabolism·Patricia CarrascoNúria Casals

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