Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-Recessive Complete Congenital Stationary Night Blindness

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• 作者：Isabelle Audo¹ ; ² ; ³ ; ⁴ ; ⁵ ; ³⁹ ; Kinga Bujakowska¹ ; ² ; ³ ; ³⁹ ; Elise Orhan¹ ; ² ; ³ ; Charlotte  ; M. Poloschek⁶ ; Sabine Defoort-Dhellemmes⁷ ; Isabelle Drumare⁷ ; Susanne Kohl⁸ ; Tien  ; D. Luu⁹ ; Odile Lecompte⁹ ; Eberhart Zrenner¹⁰ ; Marie-Elise Lancelot¹ ; ² ; ³ ; Aline Antonio¹ ; ² ; ³ ; ⁴ ; Aurore Germain¹ ; ² ; ³ ; Christelle Michiels¹ ; ² ; ³ ; Claire Audier¹ ; ² ; ³ ; Mé ; lanie Letexier¹¹ ; Jean-Paul Saraiva¹¹ ; Bart  ; P. Leroy¹² ; ¹³ ; Francis  ; L. Munier¹⁴ ; Saddek Mohand-Saï ; d¹ ; ² ; ³ ; ⁴ ; Birgit Lorenz¹⁵ ; Christoph Friedburg¹⁵ ; Markus Preising¹⁵ ; Ulrich Kellner¹⁶ ; Agnes  ; B. Renner¹⁷ ; Veselina Moskova-Doumanova¹ ; ² ; ³ ; Wolfgang Berger¹⁸ ; ¹⁹ ; ²⁰ ; Bernd Wissinger⁸ ; Christian  ; P. Hamel²¹ ; Daniel  ; F. Schorderet²² ; Elfride De  ; Baere¹² ; Dror Sharon²³ ; Eyal Banin²³ ; Samuel  ; G. Jacobson²⁴ ; Dominique Bonneau²⁵ ; Xavier Zanlonghi²⁶ ; Guylene Le  ; Meur²⁷ ; Ingele Casteels²⁸ ; Robert Koenekoop²⁹ ; Vernon  ; W. Long³⁰ ; Francoise Meire³¹ ; Katrina Prescott³² ; Thomy de  ; Ravel³³ ; Ian Simmons³⁰ ; Hoan Nguyen⁹ ; Hé ; lè ; ne Dollfus³⁴ ; ³⁵ ; Olivier Poch⁹ ; Thierry Lé ; veillard¹ ; ² ; ³ ; Kim Nguyen-Ba-Charvet¹ ; ² ; ³ ; José ; -Alain Sahel¹ ; ² ; ³ ; ⁴ ; ⁵ ; ³⁶ ; ³⁷ ; Shomi  ; S. Bhattacharya¹ ; ² ; ³ ; ⁵ ; ³⁸ ; Christina Zeitz¹ ; ² ; ³ ; ^{christina.zeitz@inserm.fr}
• 刊名：The American Journal of Human Genetics
• 出版年：2012
• 出版时间：10 February 2012
• 年：2012
• 卷：90
• 期：2
• 页码：321-330
• 全文大小：828 K

文摘

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 (OPL) 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.1807C>T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs^{?/sup>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 OPL in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and M¨¹ller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated.}