title: Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness.
abstract: Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease-causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, re-investigation of the clinical data corrected the diagnosis to Riggs-form of CSNB. Targeted next-generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert-Bornschein-type of CSNB. This confirms that SLC24A1 defects lead to CSNB and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Neuillé
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: S
authors.initials: S
authors.lastname: Malaichamy
authors.affiliation: Ophthalmology Section, Department of Experimental Medicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vadalà
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Michiels
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Condroyer
authors.affiliation: Department of Optometry, Medical Research Foundation, Chennai, India.
authors.forename: R
authors.initials: R
authors.lastname: Sachidanandam
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: S
authors.initials: S
authors.lastname: Srilekha
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: T
authors.initials: T
authors.lastname: Arokiasamy
authors.affiliation: IntegraGen SA, Evry, France.
authors.forename: M
authors.initials: M
authors.lastname: Letexier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Démontant
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 CIC 1423, Paris, France.|Institute of Ophthalmology, University College of London, London, UK.|Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.|Académie des Sciences, Institut de France, Paris, France.
authors.forename: J-A
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Department of Vitreo-Retinal Services, Medical Research Foundation, Chennai, India.
authors.forename: P
authors.initials: P
authors.lastname: Sen
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 CIC 1423, Paris, France.|Institute of Ophthalmology, University College of London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Audo
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: N
authors.initials: N
authors.lastname: Soumittra
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Zeitz
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009216:Myopia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D019831:Sodium-Calcium Exchanger / Q000235:genetics*
chemical_list: D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger
keywords: SLC24A1; congenital stationary night blindness; high-throughput sequencing; humans