A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene.

. Purpose: To describe the clinical phenotype and the molecular pathology in a group of patients with congenital stationary night blindness due to mutations in GRM6, a gene encoding the ON bipolar metabotropic glutamate receptor 6 (mGluR6). Methods: Nine patients from seven families (age range, 7-75; median, 10 years) with a clinical diagnosis of autosomal recessive complete congenital stationary night blindness were ascertained. Clinical examination, imaging and electrophysiological assessment were performed. The coding region and intron-exon boundaries of GRM6 were sequenced. Results: The median visual acuity for the cohort was 0.2 logMAR (range 0-3). Most patients had myopic astigmatism with the median spherical equivalent being −5.375 dioptres (−0.125 to −18.75). Fundoscopy was within normal limits in 15 eyes; there was severe myopic maculopathy in three eyes. Other secondary complications included face turn because of nystagmus and strabismic amblyopia. All patients had electronegative dark-adapted bright white flash electroretinograms (ERGs) consistent with dysfunction occurring postphototransduction. In the two oldest subjects (aged 75 and 58 years), there was additional photoreceptor dysfunction in keeping with myopic degeneration. ON-OFF ERGs showed generalized cone ON bipolar system dysfunction in all five patients tested. Pattern ERG P50 was normal ( Ν = 1), subnormal ( N = 2) or undetectable ( N = 2). Nine mutations in GRM6 were detected in all seven families; six of these changes were novel. Conclusions: The phenotype associated with GRM6 mutation is variable in terms of presentation, refractive error, visual acuity and macular function. ERGs are electronegative and suggest ON-pathway dysfunction. [ABSTRACT FROM AUTHOR]