title: Targeted next generation sequencing identifies novel mutations in RP1 as a relatively common cause of autosomal recessive rod-cone dystrophy.
abstract: We report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD) and RP1 mutations. Detailed ophthalmic examination was performed in 242 sporadic and arRCD subjects. Genomic DNA was investigated using our customized next generation sequencing panel targeting up to 123 genes implicated in inherited retinal disorders. Stringent filtering coupled with Sanger sequencing and followed by cosegregation analysis was performed to confirm biallelism and the implication of the most likely disease causing variants. Sequencing identified 9 RP1 mutations in 7 index cases. Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes. Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD. Our prevalence studies showed that RP1 mutations account for up to 2.5% of arRCD. These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD. It further highlights the interest of unbiased sequencing technique, which allows investigating the implication of the same gene in different modes of inheritance. Finally, it reports that different regions of RP1 can also lead to arRCD.
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Said
authors.initials: S
authors.lastname: El Shamieh
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Boulanger-Scemama
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Lancelot
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Démontant
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Condroyer
authors.affiliation: IntegraGen SA, Genopole Campus 1, Building G8, 91030 Evry, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Letexier
authors.affiliation: IntegraGen SA, Genopole Campus 1, Building G8, 91030 Evry, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saraiva
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, 75012 Paris, France.
authors.forename: Saddek
authors.initials: S
authors.lastname: Mohand-Saïd
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, 75012 Paris, 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, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, 75012 Paris, France ; University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
mesh_terms: D000328:Adult; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human