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Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease.
Garcia-Consuegra, Ines; Blázquez, Alberto; Rubio, Juan Carlos; Arenas, Joaquín; Ballester-Lopez, Alfonsina; González-Quintana, Adrián; Andreu, Antoni L; Pinós, Tomàs; Coll-Cantí, Jaume; Lucia, Alejandro; Nogales-Gadea, Gisela; Martín, Miguel A.
Afiliação
  • Garcia-Consuegra I; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.
  • Blázquez A; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
  • Rubio JC; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Arenas J; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.
  • Ballester-Lopez A; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
  • González-Quintana A; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Andreu AL; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.
  • Pinós T; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
  • Coll-Cantí J; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Lucia A; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.
  • Nogales-Gadea G; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
  • Martín MA; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
Genet Med ; 18(11): 1128-1135, 2016 11.
Article em En | MEDLINE | ID: mdl-26913921
PURPOSE: McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs). METHODS: We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients. RESULTS: Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies. CONCLUSION: We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.Genet Med 18 11, 1128-1135.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Depósito de Glicogênio Tipo V / Glicogênio Fosforilase Muscular / Patologia Molecular Tipo de estudo: Diagnostic_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Depósito de Glicogênio Tipo V / Glicogênio Fosforilase Muscular / Patologia Molecular Tipo de estudo: Diagnostic_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article