Night Blindness, Congenital Stationary, Type 1d

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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 this form of complete congenital stationary night blindness is caused by homozygous mutation in the SLC24A1 gene (603617) on chromosome 15q22.

Description

CSNB1D is an autosomal recessive form of congenital stationary night blindness that is characterized by a Riggs type of electroretinogram (proportionally reduced a- and b-waves). Patients with Riggs-type CSNB have visual acuity within the normal range and no symptoms of myopia and/or nystagmus (summary by Riazuddin et al., 2010).

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

Clinical Features

Riazuddin et al. (2010) studied 5 affected individuals from 4 sibships of a large consanguineous Pakistani pedigree from the Punjab province who reported night blindness with normal daytime vision since early childhood. Detailed ocular examination in 4 of the 5 individuals revealed no obvious anomalies on funduscopic examination, with no macular atrophy, no pigment deposition, and no vascular attenuation. Full-field ERGs showed absence of a- and b-waves under scotopic conditions for all 4 patients examined; in 2 of the patients, cone responses were modestly reduced under photopic conditions, whereas in the other 2 patients, cone responses were indistinguishable from those of an unaffected family member. Riazuddin et al. (2010) stated that the appearance of the fundus together with the ERG results of rod response were strongly suggestive of CSNB with a Riggs type of ERG, which previously had been described in only a few patients with an autosomal dominant form of CSNB.

Neuille et al. (2016) reported 4 male patients from 3 unrelated families with a Riggs form of congenital stationary night blindness. Two brothers were affected in family 1. The 6-year-old proband reportedly had night blindness since early childhood. Visual acuity was 20/20 for both eyes, with no signs of myopia or nystagmus. Fundus examination revealed no retinal or disc abnormalities. Color sensitivity was normal. Scotopic ERG responses were severely reduced for both a- and b-waves for both eyes, whereas photopic responses were normal. The probands in families 2 and 3, aged 32 and 36 years, respectively, also had night blindness since early childhood, showed no signs of reduced visual acuity, myopia, or nystagmus, and had normal color vision. Fundus examination revealed no retinal or disc abnormalities. No retinal degeneration was detected by SD-OCT. Scotopic ERG amplitudes were severely reduced in both patients. The proband in family 2 displayed minimal decreased amplitudes in response to a single photopic flash with moderately reduced flicker responses. The photopic responses of the proband of family 3 were more altered with the amplitude of the b-wave, which was significantly reduced in response to both the single flash as well as flicker.

Mapping

Riazuddin et al. (2010) performed a genomewide scan in 5 affected and 20 unaffected members of a large consanguineous Pakistani pedigree with CSNB and obtained a 2-point lod score of 4.81 with marker D15S153 (theta = 0.0). Recombination events and haplotype analysis narrowed the critical region to a 10.41-cM (6.53-Mb) interval flanked by markers D15S974 and D15S1025 on chromosome 15q22.2-q26.1.

Molecular Genetics

In affected members of a large consanguineous Pakistani pedigree with CSNB mapping to chromosome 15q22.2-q26.1, Riazuddin et al. (2010) analyzed candidate genes and identified homozygosity for a 2-bp deletion in the SLC24A1 gene (603617.0001). The mutation segregated with disease in the family and was not found in 384 control chromosomes from the Punjab province of Pakistan or in 192 chromosomes of northern European descent. Riazuddin et al. (2010) analyzed the SLC24A1 gene in another 16 probands with CSNB but found no additional pathogenic mutations.

In affected members of 3 families with CSNB1D, Neuille et al. (2016) identified homozygous or compound heterozygous mutations in the CSNB1D gene (603617.0002-603617.0005). The mutations were identified by whole-exome sequencing or next-generation sequencing after mutations in genes known to cause CSNB were excluded. No functional studies were performed.