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Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness

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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.
Keywords
GRM6 GENE, MGLUR6, PROTEIN, CHANNEL SUBUNIT, LEUCINE-RICH REPEAT, RETINITIS-PIGMENTOSA, COMPLETE FORM, BIPOLAR CELLS, HIGH MYOPIA, TRPM1

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Citation

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Chicago
Zeitz, Christina, Samuel G Jacobson, Christian P Hamel, Kinga Bujakowska, Marion Neuillé, Elise Orhan, Xavier Zanlonghi, et al. 2013. “Whole-exome Sequencing Identifies LRIT3 Mutations as a Cause of Autosomal-recessive Complete Congenital Stationary Night Blindness.” American Journal of Human Genetics 92 (1): 67–75.
APA
Zeitz, C., Jacobson, S. G., Hamel, C. P., Bujakowska, K., Neuillé, M., Orhan, E., Zanlonghi, X., et al. (2013). Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. AMERICAN JOURNAL OF HUMAN GENETICS, 92(1), 67–75.
Vancouver
1.
Zeitz C, Jacobson SG, Hamel CP, Bujakowska K, Neuillé M, Orhan E, et al. Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. AMERICAN JOURNAL OF HUMAN GENETICS. 2013;92(1):67–75.
MLA
Zeitz, Christina, Samuel G Jacobson, Christian P Hamel, et al. “Whole-exome Sequencing Identifies LRIT3 Mutations as a Cause of Autosomal-recessive Complete Congenital Stationary Night Blindness.” AMERICAN JOURNAL OF HUMAN GENETICS 92.1 (2013): 67–75. Print.
@article{4083644,
  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.},
  author       = {Zeitz, Christina and Jacobson, Samuel G and Hamel, Christian P and Bujakowska, Kinga and Neuillé, Marion and Orhan, Elise and Zanlonghi, Xavier and Lancelot, Marie-Elise and Michiels, Christelle and Schwartz, Sharon B and Bocquet, Béatrice and Antonio, Aline and Audier, Claire and Letexier, Mélanie and Saraiva, Jean-Paul and Luu, Tien D and Sennlaub, Florian and Nguyen, Hoan and Poch, Olivier and Dollfus, Hélène and Lecompte, Odile and Kohl, Susanne and Sahel, José-Alain and Bhattacharya, Shomi S and Audo, Isabelle and Congenital Stationary Night Blindness Consortium, the and De Baere, Elfride and Leroy, Bart},
  issn         = {0002-9297},
  journal      = {AMERICAN JOURNAL OF HUMAN GENETICS},
  keywords     = {GRM6 GENE,MGLUR6,PROTEIN,CHANNEL SUBUNIT,LEUCINE-RICH REPEAT,RETINITIS-PIGMENTOSA,COMPLETE FORM,BIPOLAR CELLS,HIGH MYOPIA,TRPM1},
  language     = {eng},
  number       = {1},
  pages        = {67--75},
  title        = {Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2012.10.023},
  volume       = {92},
  year         = {2013},
}

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