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Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness

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Abstract
Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway Mutations in NYX, GRM6, and TRPM1, expressed in the outer plexiform layer (Oft) lead to disruption of the ON-bipolar cell response and have been seen in patients with cCSNB. Whole-exome sequencing in cCSNB patients lacking mutations in the known genes led to the identification of a homozygous missense mutation (c.1.807C>T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs*57]) in a simplex male cCSNB patient. Additional screening with Sanger sequencing of 40 patients identified three other cCSNB patients harboring additional allelic mutations in GPR179. Although, immunhistological studies revealed Gpr179 in the OM in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and Muller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated.
Keywords
CGMP-PHOSPHODIESTERASE, BIPOLAR CELLS, MUSCULAR-DYSTROPHY, PHENOTYPIC IMPACT, CHANNEL SUBUNIT, CONE DYSTROPHY, GAMMA-SUBUNIT, COMPLETE FORM, MOUSE RETINA, PROTEIN

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Chicago
Audo, Isabelle, Kinga Bujakowska, Elise Orhan, Charlotte M Poloschek, Sabine Defoort-Dhellemmes, Isabelle Drumare, Susanne Kohl, et al. 2012. “Whole-exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-recessive Complete Congenital Stationary Night Blindness.” American Journal of Human Genetics 90 (2): 321–330.
APA
Audo, Isabelle, Bujakowska, K., Orhan, E., Poloschek, C. M., Defoort-Dhellemmes, S., Drumare, I., Kohl, S., et al. (2012). Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. AMERICAN JOURNAL OF HUMAN GENETICS, 90(2), 321–330.
Vancouver
1.
Audo I, Bujakowska K, Orhan E, Poloschek CM, Defoort-Dhellemmes S, Drumare I, et al. Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. AMERICAN JOURNAL OF HUMAN GENETICS. 2012;90(2):321–30.
MLA
Audo, Isabelle, Kinga Bujakowska, Elise Orhan, et al. “Whole-exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-recessive Complete Congenital Stationary Night Blindness.” AMERICAN JOURNAL OF HUMAN GENETICS 90.2 (2012): 321–330. Print.
@article{2086373,
  abstract     = {Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway Mutations in NYX, GRM6, and TRPM1, expressed in the outer plexiform layer (Oft) lead to disruption of the ON-bipolar cell response and have been seen in patients with cCSNB. Whole-exome sequencing in cCSNB patients lacking mutations in the known genes led to the identification of a homozygous missense mutation (c.1.807C{\textrangle}T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs*57]) in a simplex male cCSNB patient. Additional screening with Sanger sequencing of 40 patients identified three other cCSNB patients harboring additional allelic mutations in GPR179. Although, immunhistological studies revealed Gpr179 in the OM in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and Muller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated.},
  author       = {Audo, Isabelle and Bujakowska, Kinga and Orhan, Elise and Poloschek, Charlotte M and Defoort-Dhellemmes, Sabine and Drumare, Isabelle and Kohl, Susanne and Luu, Tien D and Lecompte, Odile and Zrenner, Eberhart and Lancelot, Marie-Elise and Antonio, Aline and Germain, Aurore and Michiels, Christelle and Audier, Claire and Letexier, M{\'e}lanie and Saraiva, Jean-Paul and Leroy, Bart and Munier, Francis L and Mohand-Sa{\"i}d, Saddek and Lorenz, Birgit and Friedburg, Christoph and Preising, Markus and Kellner, Ulrich and Renner, Agnes B and Moskova-Doumanova, Veselina and Berger, Wolfgang and Wissinger, Bernd and Hamel, Christian R and Schorderet, Daniel F and De Baere, Elfride and Sharon, Dror and Banin, Eyal and Jacobson, Samuel G and Bonneau, Dominique and Zanlonghi, Xavier and Le Meur, Guylene and Casteels, Ingele and Koenekoop, Robert and Long, Vernon W and Meire, Fran\c{c}oise and Prescott, Katrina and de Ravel, Thomy and Simmons, Ian and Nguyen, Hoan and Dollfus, H{\'e}l{\`e}ne and Poch, Olivier and L{\'e}veillard, Thierry and Nguyen-Ba-Charvet, Kim and Sahel, Jos{\'e}-Alain and Bhattacharya, Shomi S and Zeitz, Christina},
  issn         = {0002-9297},
  journal      = {AMERICAN JOURNAL OF HUMAN GENETICS},
  keyword      = {CGMP-PHOSPHODIESTERASE,BIPOLAR CELLS,MUSCULAR-DYSTROPHY,PHENOTYPIC IMPACT,CHANNEL SUBUNIT,CONE DYSTROPHY,GAMMA-SUBUNIT,COMPLETE FORM,MOUSE RETINA,PROTEIN},
  language     = {eng},
  number       = {2},
  pages        = {321--330},
  title        = {Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2011.12.007},
  volume       = {90},
  year         = {2012},
}

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