Night Blindness, Congenital Stationary, Type 1g

A number sign (#) is used with this entry because of evidence that congenital stationary night blindness type 1G (CSNB1G) is caused by homozygous mutation in the GNAT1 gene (139330) on chromosome 3p21.

An autosomal dominant form of CSNB (CSNBAD3; 610444) is also caused by mutation in the GNAT1 gene.

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

Clinical Features

Naeem et al. (2012) studied 4 affected members of a consanguineous Pakistani family who all reported an inability to see at night from early childhood. Visual acuity and color vision were normal, and fundus photographs showed no signs of retinal artery attenuation or bone spicule pigmentation. Electroretinograms (ERGs) revealed reduced or nearly absent a- and b-waves, even after 4 hours of dark adaptation. The 30-Hz flicker recordings representing isolated cone responses were normal, although the amplitudes of those recordings were reduced compared to an unaffected family member. Scotopic ERG recordings measured at -25 dB were absent.

Carrigan et al. (2016) reported an 80-year-old Irish man who had a lifelong history of unchanging night blindness, but presented due to 'difficulty with steps' for the previous 6 months. Ocular examination revealed good visual acuity and normal corneas, anterior segments, and lenses. Color vision was normal. Fundus examination showed slight disc pallor and arteriolar attenuation in both eyes, with marked peripheral pigmentary deposits, some of which had a bone-spicule appearance and some of which were clumping in nature. The maculae appeared healthy. Visual field testing showed constriction of visual fields consistent with retinitis pigmentosa. Full-field ERGs showed a lack of rod phototransduction, with nonrecordable dark-adapted rod-isolated responses. Significantly attenuated dark-adapted responses, likely cone-driven, were seen with the maximal intensity flash. significantly attenuated light-adapted cone-isolated responses were observed. Carrigan et al. (2016) noted that this ERG pattern was similar to that previously reported in patients with autosomal recessive and autosomal dominant GNAT1-associated CSNB. The proband's 56-year-old daughter had no eye-related complaints and normal funduscopic, visual field, and ERG findings.

Mapping

Following exclusion of the CABP4 (608965), GRM6 (604096), and SLC24A1 (603617) loci in a consanguineous Pakistani family segregating autosomal recessive CSNB, Naeem et al. (2012) performed a genomewide scan that yielded a maximum 2-point lod score of 3.09 (theta = 0) at chromosome 3p22.1-p14.3, between markers D3S3522 and D3S1289. Fine mapping revealed a 2-point lod score of 3.12 at D3S3624, and recombination events narrowed the critical interval to a 6.15-cM (13.57-Mb) region flanked by markers D3S3658 proximally and D3S1289 distally.

Molecular Genetics

In all 4 affected members of a consanguineous Pakistani family with autosomal recessive CSNB mapping to chromosome 3p22.1-p14.3, Naeem et al. (2012) identified homozygosity for a missense mutation in the GNAT1 gene (D129G; 139330.0003). Unaffected family members were heterozygous for the mutation, which was not found in 192 ethnically matched control chromosomes.

In a next-generation sequencing study of 191 Irish patients with retinal degeneration, including 4 who were diagnosed with CSNB, Carrigan et al. (2016) identified a nonsense mutation in the GNAT1 gene (Q302X; 139330.0004) in an 80-year-old man with lifelong nonprogressive night blindness who also exhibited late-onset mild localized retinitis pigmentosa. The proband was negative for mutation in 181 other retinopathy-associated genes. The Q302X mutation, which was detected in heterozygosity in his unaffected 56-year-old daughter, was not found in the 1000 Genomes Project database; however, it was present at a low allele frequency of 5/66,210 in the ExAC database. Noting that previously reported patients with GNAT1-associated CSNB did not show the pigmentary disturbances observed in this patient, Carrigan et al. (2016) suggested that retinal degeneration might develop as those patients advanced in age.