Night Blindness, Congenital Stationary, Type 1h

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

RHO, GRM6, TRPM1, GNAT1, LRIT3, SLC24A1, PDE6B, GPR179, SAG, CACNA1F, NYX, CABP4, GNB3, CACNA2D4, GRK1, RDH5, RBP4, TRAPPC9, USH2A, ABCA4, RPGR, RBP3, FGFR2, ERG, GRK7, RPE65, USP11, SOCS2, BBS1, GNAZ

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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A number sign (#) is used with this entry because of evidence that congenital stationary night blindness type 1H (CSNB1H) is caused by homozygous or compound heterozygous mutation in the GNB3 gene (139130) on chromosome 12p13.

Description

Congenital stationary night blindness type 1H (CSNB1H) is an unusual and unique stationary retinal disorder with a dual anomaly in visual processing, characterized by a partial or severe degree of ON bipolar dysfunction and variably reduced cone sensitivity. Patients present with childhood-onset night blindness and middle age-onset photophobia, but have near-normal vision and do not exhibit nystagmus or high myopia (Vincent et al., 2016).

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

Clinical Features

Vincent et al. (2016) studied a 3-generation Lebanese-Armenian kindred in which 2 brothers and their maternal aunt exhibited mildly reduced vision and normal fundus appearance; the 11-year-old younger brother and the 48-year-old aunt also had childhood-onset night blindness. The authors also studied a 65-year-old French woman with childhood-onset night blindness. Photophobia and color vision deficits were noted only in the 2 middle-aged patients. None of the patients had nystagmus, and all had a best-corrected visual acuity of 20/30 or better. Mild myopia was observed in 1, and 2 had hyperopia; all had normal fundus and visual fields. Visual parameters remained stable on follow-up in all cases, including 47 years of follow-up in the French woman. Vincent et al. (2016) considered these findings consistent with a diagnosis of CSNB. Electroretinography suggested partial rod ON bipolar dysfunction in the brothers, with severe dysfunction in the 2 older patients. Reduced cone sensitivity was also observed in the 2 older patients, which the authors noted was atypical in CSNB. Long-duration stimulus testing in the Lebanese-Armenian family confirmed cone OFF-pathway preservation.

Molecular Genetics

In a 3-generation Lebanese-Armenian kindred with congenital stationary night blindness in which the proband was known to be negative for mutation in 17 CSNB-associated genes and in 114 retinal dystrophy-associated genes, Vincent et al. (2016) performed whole-exome sequencing and identified homozygosity or compound heterozygosity for mutations in the GNB3 gene: 2 affected Lebanese-Armenian brothers were compound heterozygous for a nonsense mutation (W339X; 139130.0002) inherited from their unaffected Armenian mother, and an in-frame 3-bp deletion (K57del; 139130.0003) inherited from their unaffected Lebanese father. Their affected maternal aunt was homozygous for the nonsense mutation, which was present in heterozygosity in the unaffected maternal grandparents and an unaffected maternal uncle. Analysis of the GNB3 gene in 58 additional CSNB cases revealed a 65-year-old French woman from a consanguineous family who was negative for mutation in known CSNB genes but carried a missense mutation in GNB3 (S67F; 139130.0004) that was believed to be homozygous; family members were unavailable for testing.