Night Blindness, Congenital Stationary, Type 1e

A number sign (#) is used with this entry because this form of complete congenital stationary night blindness (CSNB1E) is caused by homozygous or compound heterozygous mutation in the GPR179 gene (614515) on chromosome 17q12.

Description

Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. Individuals with cCSNB and animal models of the disorder have an ERG waveform that lacks the b-wave because of failure to transmit the photoreceptor signal through the retinal depolarizing bipolar cells (summary by Peachey et al., 2012).

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

Clinical Features

Peachey et al. (2012) studied 2 probands with complete congenital stationary night blindness (cCSNB). The first proband, who had no family history of night blindness or consanguinity, was 10 years old at the time of diagnosis. He presented with 20/70 best-corrected visual acuities, mild myopic refractive error, congenital nystagmus, a history of early-onset night blindness, normal retinal appearance, and full Goldmann visual fields. Dark-adapted ERGs showed a markedly reduced b-wave, whereas the ERG obtained to a high flash luminance had a robust a-wave without the subsequent b-wave seen in controls. Under light-adapted conditions, the ERG waveform showed a square a-wave but retained a late positive ERG component. The second proband was a woman of Norwegian descent who was 20 years old at the time of diagnosis. She presented with rotatory nystagmus, a very unusual blond fundus, congenital night blindness, and decreased visual acuity. ERGs in the second proband were similar to those of the first proband, with selective absence of the dark-adapted b-wave and a square light-adapted a-wave. Peachey et al. (2012) noted that these ERG abnormalities had been shown to be characteristic of selective dysfunction of the ON-bipolar pathway with OFF-bipolar pathway preservation by Miyake et al. (1994), thus distinguishing cCSNB from other retinal disorders with a reduced b-wave.

Molecular Genetics

In a consanguineous family of Lebanese origin in which 3 sibs had complete congenital stationary night blindness and the index patient was negative for mutation in the GRM6 (604096) and TRPM1 (603576) genes, Audo et al. (2012) performed whole-exome sequencing and identified homozygosity for a missense mutation in the GPR179 gene (H603Y; 614515.0001) that segregated with the disorder. Whole-exome sequencing in a male CSNB patient of Portuguese origin revealed homozygosity for a 1-bp deletion in GPR179 (278delC; 614515.0002). Subsequent analysis of the GPR179 gene in 40 CSNB patients revealed 3 additional patients with compound heterozygous mutations (see, e.g., 614515.0003-614515.0004).

Peachey et al. (2012) analyzed the candidate gene GPR179 in 44 cCSNB patients lacking depolarizing bipolar cell (DBC) function and identified 2 probands with compound heterozygosity for inactivating mutations in GPR179 (see 614515.0005-614515.0007).