title: Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Garcia-Consuegra
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alberto
authors.identifier: 0000-0002-6479-3615
authors.initials: A
authors.lastname: Blázquez
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Rubio
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain.
authors.forename: Alfonsina
authors.initials: A
authors.lastname: Ballester-Lopez
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Adrián
authors.identifier: 0000-0002-4011-362X
authors.initials: A
authors.lastname: González-Quintana
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: Antoni L
authors.initials: AL
authors.lastname: Andreu
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.|Institut de Recerca Val d'Hebron, Barcelona, Spain.
authors.forename: Tomàs
authors.initials: T
authors.lastname: Pinós
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain.|Unidad Neuromuscular, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Coll-Cantí
authors.affiliation: Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Universidad Europea, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain.
authors.forename: Gisela
authors.identifier: 0000-0002-7414-212X
authors.initials: G
authors.lastname: Nogales-Gadea
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Miguel A
authors.identifier: 0000-0003-4741-772X
authors.initials: MA
authors.lastname: Martín
mesh_terms: D000293:Adolescent; D000328:Adult; D018389:Codon, Nonsense / Q000235:genetics; D005260:Female; D024982:Glycogen Phosphorylase, Muscle Form / Q000097:blood* / Q000235:genetics; D006012:Glycogen Storage Disease Type V / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D057089:Pathology, Molecular / Q000379:methods*; D012326:RNA Splicing / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D024982:Glycogen Phosphorylase, Muscle Form