Night Blindness, Congenital Stationary, Autosomal Dominant 2

A number sign (#) is used with this entry because of evidence that autosomal dominant congenital stationary night blindness-2 (CSNBAD2) is caused by heterozygous mutation in the PDE6B gene (180072) on chromosome 4p16.

For a general phenotypic description and discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).

Clinical Features

Rambusch (1909) described a large Danish kindred with autosomal dominant congenital stationary night blindness (CSNB). The ancestor of the family was a farmer born about 1660 in northern Jutland. At the time of the report by Rosenberg et al. (1991), the pedigree comprised more than 200 affected persons in 11 generations. Gal et al. (1994) summarized the findings. Autosomal dominant inheritance was substantiated by several instances of male-to-male transmission. Penetrance was complete. Expression of the mutant allele seemed to be uniform; affected members complained of lack of night vision for as long as they could remember. Ophthalmoscopy revealed no signs of retinitis pigmentosa (see 268000). Dark adaptation curves were monophasic, due to the absence of the rod phase, with final thresholds elevated approximately by a factor of 10(3). Day vision was normal in all patients. Rod responses following full-field single-flash stimulation with a dim blue light were absent, while mixed cone-rod responses to white suprathreshold stimuli were strongly attenuated. The residual b-wave had a shape and temporal characteristics of a cone response with superimposed oscillatory potentials. The a-wave amplitude was reduced to 30 to 50% of the lower normal limit, while implicit time was normal. Cone responses to 32-Hz flickering white light were normal. Both electrophysiologic and psychophysical findings in affected family members were identical to those reported in patients from the Nougaret family (see 610444), in whom mutations in the GNAT1 gene (139330) were found.

Tsang et al. (2007) reported a 36-year-old man with a long history of CSNB and myopia. ERG showed generalized retinal dysfunction affecting the rod system and a locus of dysfunction at the rod-bipolar interface. There was little change in 10 years and no evidence of photoreceptor cell death. There was a family history of the disorder; genetic analysis identified a mutation in the PDE6B gene (H258N; 180072.0005).

Mapping

Gal et al. (1994) mapped the CSNB phenotype in the Rambusch kindred to chromosome 4p16.3 by linkage studies.

Molecular Genetics

In affected members of a large Danish family, referred to as the Rambusch pedigree, with CSNG linked to chromosome 4p16.3, Gal et al. (1994) identified a heterozygous missense mutation (H258N; 180072.0005) in the PDE6B gene. Gal et al. (1994) hypothesized that the mutation impeded complete inactivation of phosphodiesterase in dark-adapted photoreceptors, thus leading to CSNB.