Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA

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dc.contributor.author García-Consuegra, Inés spa
dc.contributor.author Rubio, Juan Carlos spa
dc.contributor.author Nogales-Gadea, Gisela spa
dc.contributor.author Bautista, José M. spa
dc.contributor.author Jiménez Sáiz, Sergio Lorenzo spa
dc.contributor.author Cabello Sánchez, Ana Belén spa
dc.contributor.author Lucía Mulas, Alejandro spa
dc.contributor.author Andreu, Antoni L. spa
dc.contributor.author Arenas, Joaquín spa
dc.contributor.author Martín, Miguel Ángel spa
dc.date.accessioned 2013-11-27T17:26:29Z
dc.date.available 2013-11-27T17:26:29Z
dc.date.issued 2009 spa
dc.identifier.citation García-Consuegra, I., Rubio, J. C., Nogales-Gadea, G., Bautista, J. M., Jiménez-Sáiz, S., Cabello-Sánchez, A. B., ..., & Martín, M. A. (2009). Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA. Journal of Medical Genetics, 46(3), 198-202. spa
dc.identifier.issn 14686244 spa
dc.identifier.uri http://hdl.handle.net/11268/764
dc.description.abstract Objective: Methods: Results: Conclusions: To identify pathogenic mutant alleles of the PYGM gene in "genetic manifesting heterozygous" patients with McArdle disease-that is, those in whom we could only find a sole mutant allele by genomic DNA analysis.We studied four unrelated patients. PCR-RFLP, gene sequencing, and muscle cDNA analysis were performed to search for mutations in the PYGM gene. The effects of the mutations were evaluated by in silico analysis, and gene expression was assessed by real-time polymerase chain reaction (PCR).Patient 1 was a compound heterozygous for the p.G205S missense mutation and for a novel "in frame" mutation, p.Q176_M177insVQ, resulting from a retention of six nucleotides from the 3'-end sequence of intron 4. Patient 2 was heterozygous for the common nonsense mutation p.R50X, and for a 1094 bp, c.1969+214_2177+369del mutation, spanning from intron 16 to intron 17 sequences. Furthermore, mRNA expression level was dramatically reduced consistent with nonsense mediated decay. Patient 3 was heterozygous for the p.R50X substitution, and patient 4 was heterozygous for the relatively common private Spanish mutation p.W798R. These two patients harboured a heterozygous exonic synonymous variant, p.K215K. Quantification of gene transcripts in patient 3 revealed a drastic decrease in the relative expression of the gene, which strongly supports the possibility of nonsense mediated decay.Our results indicate that skeletal muscle cDNA studies in "genetic manifesting heterozygous" patients with McArdle disease are prone to identify their second mutant allele. spa
dc.language.iso eng spa
dc.subject.other Mutation* spa
dc.subject.other Glycogen Phosphorylase, Muscle Form/*Genetics spa
dc.subject.other Glycogen Storage Disease Type V/*Genetics spa
dc.subject.other Muscle, Skeletal/*Metabolism spa
dc.subject.other Rna, Messenger/*Analysis spa
dc.subject.other Computer Simulation spa
dc.subject.other Gene Expression spa
dc.subject.other Glycogen Phosphorylase, Muscle Form/Metabolism spa
dc.subject.other Glycogen Storage Disease Type V/Pathology spa
dc.subject.other Heterozygote spa
dc.subject.other Humans spa
dc.subject.other Male spa
dc.subject.other Middle Aged spa
dc.subject.other Polymerase Chain Reaction spa
dc.subject.other Polymorphism, Restriction Fragment Length spa
dc.subject.other Rna, Messenger/Genetics spa
dc.subject.other Sequence Analysis, Dna spa
dc.title Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA spa
dc.type article spa
dc.description.impact 5.751 JCR (2009) Q1, 19/146 Genetics & heredity spa
dc.identifier.doi 10.1136/jmg.2008.059469 spa
dc.rights.accessRights openAccess en
dc.subject.unesco Fisiología humana spa
dc.subject.unesco Enfermedad nutricional spa
dc.description.filiation UEM spa
dc.peerreviewed Si spa

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