Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Nov 7.
doi: 10.1007/s10633-025-10062-x. Online ahead of print.

Incomplete congenital stationary night blindness associated with a novel variant in the CACNA1F gene

Shi Pei Loo  1 , Chloe Shipton  2 , Mark Hamilton  3 , Andrew Brown  2 , Eoghan Millar  1 , Iqbal Malik  4 , Madeleine Craig  4 , Ruth Hamilton  5   6
Affiliations

Incomplete congenital stationary night blindness associated with a novel variant in the CACNA1F gene

Shi Pei Loo et al. Doc Ophthalmol. .

Abstract

Purpose: Incomplete congenital stationary night blindness (icCSNB) is a subtype of inherited, non-progressive retinal diseases. Most cases of icCSNB result from mutations in the X-linked gene CACNA1F. We describe the clinical findings of two male siblings diagnosed with icCSNB, both carrying a novel variant c.4008 + 5G > T in CACNA1F inherited from their mother.

Methods: We carried out a comprehensive ophthalmic assessment, including fundus imaging, optical coherence tomography (OCT) scanning and electroretinography. We performed genetic testing with next generation sequencing, in-silico and functional analyses to further characterise the novel variant.

Results: Two male siblings presented with high myopia and reduced visual acuities at age three. Examination and OCT demonstrated no significant abnormalities in both siblings. Full-field electroretinogram (ffERG) testing demonstrated markedly reduced amplitude to weak flashes and an electronegative waveform to strong flashes in dark-adapted ERGs, resembling that of icCSNB, leading to its diagnosis in both children. Next generation sequencing in the older sibling identified a novel hemizygous c.4008 + 5G > T variant in CACNA1F. In-silico analysis of this variant predicted that it would disrupt normal splicing of CACNA1F, though it was not possible to confirm this by RNA sequencing. This same variant was found in the younger sibling, as well as in their mother who had normal examination and ffERG findings.

Conclusions: We report a novel CACNA1F variant not previously identified in the literature in three patients. Although functional analyses were unable to confirm pathogenicity of this variant, in-silico tools predicted that its effect is consistent with the pathogenesis of icCSNB. Reporting of this family further widens the genotypic spectrum of icCSNB.

Keywords: Electroretinography; Incomplete congenital stationary night blindness; Next generation sequencing; Novel CACNA1F mutation.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: All authors certify that they have no conflicts of interest. Ethical approval: Ethical opinion was obtained from the West of Scotland Research Ethics Service, which confirmed that no ethical approval is required as this case series was not considered research by the NHS. The management of these patients was not altered for this case series. This case series was conducted in accordance with the ethical standards of the institutional research committee (West of Scotland Research Ethics Service) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all patients included in this study. Statement on the welfare of animals: No animal experiments were performed in this study. Statement of human rights: Ethical opinion was obtained from the West of Scotland Research Ethics Service, which confirmed that no ethical approval is required as this case series was not considered research by the NHS. The management of these patients was not altered for this case series. This case series was conducted in accordance with the ethical standards of the institutional research committee (West of Scotland Research Ethics Service) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

    1. Zeitz C, Robson AG, Audo I (2015) Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms. Prog Retin Eye Res 45:58–110. https://doi.org/10.1016/j.preteyeres.2014.09.001 - DOI - PubMed
    1. De Silva SR, Arno G, Robson AG, Fakin A, Pontikos N, Mohamed MD, Bird AC, Moore AT, Michaelides M, Webster AR, Mahroo OA (2021) The X-linked retinopathies: physiological insights, pathogenic mechanisms, phenotypic features and novel therapies. Prog Retin Eye Res 82:100898. https://doi.org/10.1016/j.preteyeres.2020.100898 - DOI - PubMed
    1. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30 - DOI - PubMed - PMC
    1. Robson AG, Frishman LJ, Grigg J, Hamilton R, Jeffrey BG, Kondo M, Li S, McCulloch DL (2022) ISCEV standard for full-field clinical electroretinography (2022 update). Doc Ophthalmol 144(3):165–177. https://doi.org/10.1007/s10633-022-09872-0 - DOI - PubMed - PMC
    1. Kim AH, Liu PK, Chang YH, Kang EYC, Wang HH, Chen N, Tseng YJ, Seo GH, Lee H, Liu L, Chao AN, Chen KJ, Hwang YS, Wu WC, Lai CC, Tsang SH, Hsiao MC, Wang NK (2022) Congenital stationary night blindness: clinical and genetic features. Int J Mol Sci 23(23):14965. https://doi.org/10.3390/ijms232314965 - DOI - PubMed - PMC

LinkOut - more resources