title: Mutational spectrum of Duchenne muscular dystrophy in Spain: Study of 284 cases.
abstract: BACKGROUND
  Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons.
  
  
  METHODS
  We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations.
  
  
  RESULTS
  Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations.
  
  
  CONCLUSIONS
  The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.
authors.affiliation: Grupo de Patología Neonatal y Pediátrica, Enfermedades raras, Instituto de Investigación Biomédica de Ourense-Pontevedra-Vigo (IBI), Vigo, España; Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, España.
authors.forename: I
authors.initials: I
authors.lastname: Vieitez
authors.affiliation: Departamento de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: P
authors.initials: P
authors.lastname: Gallano
authors.affiliation: Departamento de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: L
authors.initials: L
authors.lastname: González-Quereda
authors.affiliation: Departamento de Genética, Reproducción y Medicina fetal, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: S
authors.initials: S
authors.lastname: Borrego
authors.affiliation: Departamento de Genética, Reproducción y Medicina fetal, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: I
authors.initials: I
authors.lastname: Marcos
authors.affiliation: Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: J M
authors.initials: JM
authors.lastname: Millán
authors.affiliation: Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: T
authors.initials: T
authors.lastname: Jairo
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, España.
authors.forename: C
authors.initials: C
authors.lastname: Prior
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, España.
authors.forename: J
authors.initials: J
authors.lastname: Molano
authors.affiliation: Departamento de Genética, Hospital Universitario Fundación Jiménez Díaz, Madrid, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: M J
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.affiliation: Departamento de Genética, Hospital Universitario Fundación Jiménez Díaz, Madrid, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España.
authors.forename: J
authors.initials: J
authors.lastname: Gallego-Merlo
authors.affiliation: Unidad de Genética, Hospital Universitario de Basurto, Vizcaya, España.
authors.forename: M
authors.initials: M
authors.lastname: García-Barcina
authors.affiliation: Sección de Genética Clínica, Servicio de Análisis Clínicos, Hospital Clínico San Carlos, Madrid, España.
authors.forename: M
authors.initials: M
authors.lastname: Fenollar
authors.affiliation: Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, España. Electronic address: cnavfer@sergas.es.
authors.forename: C
authors.initials: C
authors.lastname: Navarro
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
chemical_list: D016189:Dystrophin
keywords: Análisis mutacional; Diagnóstico genético; Distrofia muscular Duchenne; Duchenne muscular dystrophy; Genetic diagnosis; Multiplex ligation-dependent probe amplification; Mutational analysis; Secuenciación; Sequencing