TRPM1 Is Mutated in Patients with Autosomal-Recessive Complete Congenital Stationary Night Blindness

被引：183

作者：

Audo, Isabelle ^{[1
,2
,3
,4
,5
]}

Kohl, Susanne ^{[6
]}

Leroy, Bart P. ^{[7
,8
]}

Munier, Francis L. ^{[9
,18
]}

Guillonneau, Xavier ^{[1
,2
,3
]}

Mohand-Said, Saddek ^{[1
,2
,3
,4
]}

Bujakowska, Kinga ^{[1
,2
,3
]}

Nandrot, Emeline F. ^{[1
,2
,3
]}

Lorenz, Birgit ^{[10
,11
]}

Preising, Markus ^{[10
,11
]}

Kellner, Ulrich ^{[12
]}

Renner, Agnes B. ^{[13
]}

Bernd, Antje ^{[14
]}

Antonio, Aline ^{[1
,2
,3
,4
]}

Moskova-Doumanova, Veselina ^{[1
,2
,3
]}

Lancelot, Marie-Elise ^{[1
,2
,3
]}

Poloschek, Charlotte M. ^{[15
]}

Drumare, Isabelle ^{[16
]}

Defoort-Dhellemmes, Sabine ^{[16
]}

Wissinger, Bernd ^{[6
]}

Leveillard, Thierry ^{[1
,2
,3
]}

Hamel, Christian P. ^{[17
]}

Schorderet, Daniel F. ^{[18
]}

De Baere, Elfride ^{[7
]}

Berger, Wolfgang ^{[19
]}

Jacobson, Samuel G. ^{[20
]}

Zrenner, Eberhart ^{[14
]}

Sahel, Jose-Alain ^{[1
,2
,3
,4
]}

Bhattacharya, Shomi S. ^{[1
,2
,3
,5
]}

Zeitz, Christina ^{[1
,2
,3
]}

机构：

[1] INSERM, UMR S968, F-75012 Paris, France

[2] CNRS, UMR 7210, F-75012 Paris, France

[3] Univ Paris 06, Inst Vis, UMR S968, F-75012 Paris, France

[4] INSERM, CHNO Quinze Vingts, CMR CIC 503, F-75012 Paris, France

[5] Inst Ophthalmol, Dept Mol Genet, London EC1V 9EL, England

[6] Inst Ophthalm Res, Mol Genet Lab, D-72076 Tubingen, Germany

[7] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium

[8] Univ Ghent, Dept Ophthalmol, B-9000 Ghent, Belgium

[9] Jules Gonin Eye Hosp, Unit Oculogenet, CH-1004 Lausanne, Switzerland

[10] Univ Giessen, Dept Ophthalmol, Univ Giessen Klinikum, D-35392 Giessen, Germany

[11] Marburg GmbH, D-35392 Giessen, Germany

[12] Augen Zentrum Siegburg, D-53721 Siegburg, Germany

[13] Univ Med Ctr Regensburg, Dept Ophthalmol, D-93042 Regensburg, Germany

[14] Univ Clin Tuebingen, Univ Eye Clin, Ctr Ophthalmol, D-72076 Tubingen, Germany

[15] Univ Freiburg, Dept Ophthalmol, D-79106 Freiburg, Germany

[16] Hop Roger Salengro, CNRS, Lab Neurosci Fonct & Pathol, FRE 2726, F-59037 Lille, France

[17] Hop St Eloi, INSERM, Inst Neurosci, U583, F-34091 Montpellier, France

[18] Univ Lausanne, Inst Rech Ophtalmol, Ecole Polytech Fed Lausanne, CH-1950 Sion, Switzerland

[19] Univ Zurich, Inst Med Genet, Div Med Mol Genet & Gene Diagnost, CH-8603 Schwerzenbach, Switzerland

[20] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 85卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

METABOTROPIC RECEPTOR MGLUR6; ROD BIPOLAR CELLS; LIGHT RESPONSE; MUTATIONS; GENE; ELECTRORETINOGRAM; LOCALIZATION; PROTEIN; RICH; G-ALPHA(O);

D O I：

10.1016/j.ajhg.2009.10.013

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in similar to 60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM 1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.

引用

页码：720 / 729

页数：10

共 33 条

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