title: Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa.
abstract: Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis.
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Perez-Carro
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Corton
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Iker
authors.initials: I
authors.lastname: Sánchez-Navarro
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Zurita
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Sanchez-Bolivar
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Sánchez-Alcudia
authors.affiliation: Department of Human Genetics, Radboud university medical center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Lelieveld
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.|Grupo de Investigación en Enfermedades Neurosensoriales. Instituto de Investigación Sanitaria IIS-La Fe, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Aller
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Lopez-Martinez
authors.affiliation: Department of Ophthalmology, IIS-Fundacion Jimenez Diaz University Hospital, Madrid, Spain.
authors.forename: Ma Isabel
authors.initials: MI
authors.lastname: López-Molina
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernandez-San Jose
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.affiliation: Department of Human Genetics, Radboud university medical center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.|Grupo de Investigación en Enfermedades Neurosensoriales. Instituto de Investigación Sanitaria IIS-La Fe, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Millan
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.affiliation: Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins; D009154:Mutation; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human; C072178:RP2 protein, human; C112735:USH2A protein, human; D019204:GTP-Binding Proteins