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C. Zeitz, J.-A. Sahel, S. S. Bhattacharya, I. Audo, CSNB Study Group; TRPM1 Is Mutated in Patients With Autosomal Recessive Complete Congenital Stationary Night Blindness. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6351.
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Mutations in the genes NYX and GRM6, expressed in ON-bipolar cells, lead to a disruption of the ON-bipolar response and reduced night vision. This dysfunction is present in patients with complete congenital stationary night blindness (cCSNB). Although many cases of complete CSNB have been caused by mutations in NYX and GRM6, in ~60% of the patients the gene defect remains unknown. Here we sought to identify the disease-causing gene in the remaining patients by a candidate gene approach.
Three isoforms of TRPM1, a gene downregulated in Appaloosa horses and specifically expressed in ON-bipolar cells, were screened in 38 CSNB patients. Detailed phenotypic characterization was performed on affected family members including family history, best corrected visual acuity, ocular examination, kinetic and static perimetry, full-field and multifocal ERGs according to ISCEV standards, fundus autofluorescence and OCT imaging.
Mutation analysis of TRPM1 identified 10 unrelated cCSNB patients with 14 different mutations. The inheritance pattern appeared to be autosomal recessive based on the family information obtained from patients with TRPM1 mutations. The mutation spectrum included 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. Including the findings reported here there are now three genes associated with cCSNB. Considering the other autosomal recessive CSNB genes identified to date, TRPM1 seems to be the most frequent cause.
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