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Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy.
Birtel, Johannes; Eisenberger, Tobias; Gliem, Martin; Müller, Philipp L; Herrmann, Philipp; Betz, Christian; Zahnleiter, Diana; Neuhaus, Christine; Lenzner, Steffen; Holz, Frank G; Mangold, Elisabeth; Bolz, Hanno J; Charbel Issa, Peter.
Afiliação
  • Birtel J; Department of Ophthalmology, University of Bonn, Bonn, Germany.
  • Eisenberger T; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany.
  • Gliem M; Bioscientia Center for Human Genetics, Ingelheim, Germany.
  • Müller PL; Department of Ophthalmology, University of Bonn, Bonn, Germany.
  • Herrmann P; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany.
  • Betz C; Department of Ophthalmology, University of Bonn, Bonn, Germany.
  • Zahnleiter D; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany.
  • Neuhaus C; Department of Ophthalmology, University of Bonn, Bonn, Germany.
  • Lenzner S; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany.
  • Holz FG; Bioscientia Center for Human Genetics, Ingelheim, Germany.
  • Mangold E; Bioscientia Center for Human Genetics, Ingelheim, Germany.
  • Bolz HJ; Bioscientia Center for Human Genetics, Ingelheim, Germany.
  • Charbel Issa P; Bioscientia Center for Human Genetics, Ingelheim, Germany.
Sci Rep ; 8(1): 4824, 2018 03 19.
Article em En | MEDLINE | ID: mdl-29555955
Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar retinal phenotype, indicating a common molecular disease cause in each subgroup.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Marcadores Genéticos / Proteínas do Olho / Distrofias de Cones e Bastonetes / Degeneração Macular / Mutação Tipo de estudo: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Marcadores Genéticos / Proteínas do Olho / Distrofias de Cones e Bastonetes / Degeneração Macular / Mutação Tipo de estudo: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha