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Molecular findings from 537 individuals with inherited retinal disease.
Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; O'Sullivan, James; Williams, Simon G; Lamb, Janine A; Panda, Binay; Sergouniotis, Panagiotis I; Gillespie, Rachel L; Daiger, Stephen P; Hall, Georgina; Gale, Theodora; Lloyd, I Christopher; Bishop, Paul N; Ramsden, Simon C; Black, Graeme C M.
Afiliação
  • Ellingford JM; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Barton S; Institute of Human Development, University of Manchester, Manchester, UK.
  • Bhaskar S; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • O'Sullivan J; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Williams SG; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Lamb JA; Institute of Human Development, University of Manchester, Manchester, UK.
  • Panda B; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Sergouniotis PI; Institute of Population Health, University of Manchester, Manchester, UK.
  • Gillespie RL; Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.
  • Daiger SP; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Hall G; Institute of Human Development, University of Manchester, Manchester, UK.
  • Gale T; Manchester Royal Eye Hospital, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Lloyd IC; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
  • Bishop PN; Institute of Human Development, University of Manchester, Manchester, UK.
  • Ramsden SC; School of Public Health, University of Texas Health Science Center, Houston, Texas, USA.
  • Black GCM; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
J Med Genet ; 53(11): 761-767, 2016 Nov.
Article em En | MEDLINE | ID: mdl-27208204
BACKGROUND: Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous set of disorders, for which diagnostic second-generation sequencing (next-generation sequencing, NGS) services have been developed worldwide. METHODS: We present the molecular findings of 537 individuals referred to a 105-gene diagnostic NGS test for IRDs. We assess the diagnostic yield, the spectrum of clinical referrals, the variant analysis burden and the genetic heterogeneity of IRD. We retrospectively analyse disease-causing variants, including an assessment of variant frequency in Exome Aggregation Consortium (ExAC). RESULTS: Individuals were referred from 10 clinically distinct classifications of IRD. Of the 4542 variants clinically analysed, we have reported 402 mutations as a cause or a potential cause of disease in 62 of the 105 genes surveyed. These variants account or likely account for the clinical diagnosis of IRD in 51% of the 537 referred individuals. 144 potentially disease-causing mutations were identified as novel at the time of clinical analysis, and we further demonstrate the segregation of known disease-causing variants among individuals with IRD. We show that clinically analysed variants indicated as rare in dbSNP and the Exome Variant Server remain rare in ExAC, and that genes discovered as a cause of IRD in the post-NGS era are rare causes of IRD in a population of clinically surveyed individuals. CONCLUSIONS: Our findings illustrate the continued powerful utility of custom-gene panel diagnostic NGS tests for IRD in the clinic, but suggest clear future avenues for increasing diagnostic yields.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article