title: Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness.
abstract: Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG). The b-wave amplitude is severely reduced in the dark-adapted state of the ERG, representing abnormal function of ON bipolar cells. Furthermore, individuals with cCSNB can show other ocular features such as nystagmus, myopia, and strabismus and can have reduced visual acuity and abnormalities of the cone ERG waveform. The mode of inheritance of this form can be X-linked or autosomal recessive, and the dysfunction of four genes (NYX, GRM6, TRPM1, and GPR179) has been described so far. Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440(∗)]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384(∗)]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs(∗)59]) in the same gene. Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB. The exact role of this LRR protein in cCSNB remains to be elucidated.
authors.affiliation: Unité Mixte de Recherche S968, Institut National de la Santé et de la Recherche Médicale, F-75012 Paris, France. christina.zeitz@inserm.fr
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.forename: Kinga
authors.initials: K
authors.lastname: Bujakowska
authors.forename: Marion
authors.initials: M
authors.lastname: Neuillé
authors.forename: Elise
authors.initials: E
authors.lastname: Orhan
authors.forename: Xavier
authors.initials: X
authors.lastname: Zanlonghi
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Lancelot
authors.forename: Christelle
authors.initials: C
authors.lastname: Michiels
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.forename: Claire
authors.initials: C
authors.lastname: Audier
authors.forename: Mélanie
authors.initials: M
authors.lastname: Letexier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saraiva
authors.forename: Tien D
authors.initials: TD
authors.lastname: Luu
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.forename: Hoan
authors.initials: H
authors.lastname: Nguyen
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Odile
authors.initials: O
authors.lastname: Lecompte
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
mesh_terms: D059472:Exome; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009216:Myopia / Q000235:genetics*; D009755:Night Blindness / Q000235:genetics*; D011110:Polymorphism, Genetic; D012160:Retina / Q000737:chemistry
chemical_list: C578793:LRIT3 protein, human; D008565:Membrane Proteins