title: Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation.
abstract: BACKGROUND
  Cone and cone-rod dystrophies are clinically and genetically heterogeneous inherited retinal disorders with predominant cone impairment. They should be distinguished from the more common group of rod-cone dystrophies (retinitis pigmentosa) due to their more severe visual prognosis with early central vision loss. The purpose of our study was to document mutation spectrum of a large French cohort of cone and cone-rod dystrophies.
  
  
  METHODS
  We applied Next-Generation Sequencing targeting a panel of 123 genes implicated in retinal diseases to 96 patients. A systematic filtering approach was used to identify likely disease causing variants, subsequently confirmed by Sanger sequencing and co-segregation analysis when possible.
  
  
  RESULTS
  Overall, the likely causative mutations were detected in 62.1 % of cases, revealing 33 known and 35 novel mutations. This rate was higher for autosomal dominant (100 %) than autosomal recessive cases (53.8 %). Mutations in ABCA4 and GUCY2D were responsible for 19.2 % and 29.4 % of resolved cases with recessive and dominant inheritance, respectively. Furthermore, unexpected genotype-phenotype correlations were identified, confirming the complexity of inherited retinal disorders with phenotypic overlap between cone-rod dystrophies and other retinal diseases.
  
  
  CONCLUSIONS
  In summary, this time-efficient approach allowed mutation detection in the most important cohort of cone-rod dystrophies investigated so far covering the largest number of genes. Association of known gene defects with novel phenotypes and mode of inheritance were established.
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Boulanger-Scemama
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Said
authors.initials: S
authors.lastname: El Shamieh
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Démontant
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Condroyer
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Michiels
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Fiona
authors.initials: F
authors.lastname: Boyard
authors.affiliation: IntegraGen SA, Genopole CAMPUS 1 bat G8 FR-91030 EVRY, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saraiva
authors.affiliation: IntegraGen SA, Genopole CAMPUS 1 bat G8 FR-91030 EVRY, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Letexier
authors.affiliation: Centre Hospitalier Intercommunal de Créteil, Department of Ophthalmology, Université Paris-Est Créteil, 94000, Créteil, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Souied
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.
authors.forename: Saddek
authors.initials: S
authors.lastname: Mohand-Saïd
authors.affiliation: INSERM, U968, Paris, F-75012, France.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.|Fondation Ophtalmologique Adolphe de Rothschild, 75019, Paris, France.|Académie des Sciences-Institut de France, 75006, Paris, France.|University College London Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: INSERM, U968, Paris, F-75012, France. christina.zeitz@inserm.fr.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France. christina.zeitz@inserm.fr.|CNRS, UMR_7210, Paris, F-75012, France. christina.zeitz@inserm.fr.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
authors.affiliation: INSERM, U968, Paris, F-75012, France. isabelle.audo@inserm.fr.|Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, 17, rue Moreau, Paris, F-75012, France. isabelle.audo@inserm.fr.|CNRS, UMR_7210, Paris, F-75012, France. isabelle.audo@inserm.fr.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France. isabelle.audo@inserm.fr.|University College London Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK. isabelle.audo@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D005602:France; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics*