title: Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.
abstract: GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321*) in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321*) is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Méjécase
authors.affiliation: CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Laurent-Coriat
authors.affiliation: Institut Pasteur, Paris, France.|CNRS, UMR 3528, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Mayer
authors.affiliation: Université de Strasbourg CNRS-Icube, UMR 7357, LBGI, Faculté de Médecine, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.|CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.
authors.forename: Saddek
authors.initials: S
authors.lastname: Mohand-Saïd
authors.affiliation: CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.|Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Prévot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.|CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: Fiona
authors.initials: F
authors.lastname: Boyard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Condroyer
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Michiels
authors.affiliation: IntegraGen SA, Genopole, Campus, Evry, Paris, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Blanchard
authors.affiliation: IntegraGen SA, Genopole, Campus, Evry, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Letexier
authors.affiliation: IntegraGen SA, Genopole, Campus, Evry, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saraiva
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.|CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.|Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.|Institute of Ophthalmology, University College of London, London, United Kingdom.|Academie des Sciences, Institut de France, Paris, France.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.|CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.|Institute of Ophthalmology, University College of London, London, United Kingdom.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D000071700:Cone-Rod Dystrophies / Q000235:genetics*; D004252:DNA Mutational Analysis; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D012174:Retinitis Pigmentosa / Q000235:genetics; D015293:Transducin
chemical_list: D018389:Codon, Nonsense; C034809:GNAT1 protein, human; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin