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
Comparative Study
. 2024 Oct 3;14(1):22956.
doi: 10.1038/s41598-024-74364-x.

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

Cansu de Muijnck  1   2 , Lonneke Haer-Wigman  3 , Judith A M van Everdingen  4 , Tanya Lushchyk  4 , Pam A T Heutinck  5 , Marieke F van Dooren  6 , Anneke J A Kievit  6 , Virginie J M Verhoeven  5   6 , Marleen E H Simon  7 , Rosemarie A Wasmann  8 , Irene C Notting  9 , Elfride De Baere  10   11 , Sophie Walraedt  12 , Julie De Zaeytijd  12 , Filip Van den Broeck  12   13 , Bart P Leroy  10   12   13 , Camiel J F Boon  2   9 , Maria M van Genderen  14   15
Affiliations
Comparative Study

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

Cansu de Muijnck et al. Sci Rep. .

Abstract

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or 'wolframinopathies', exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the 'plus' phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Keywords: DOA; Inherited optic neuropathy; OPA1; Optic atrophy; WFS1.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Best-corrected binocular visual acuity (BCVA) of 20 patients per age at last follow-up.Mean BCVA was 0.42 LogMAR (20/52 Snellen), median 0.34 LogMAR (20/43 Snellen) and range 0-2. Seventy five percent of the patients had a BCVA lower than 0.58 LogMAR (20/76 Snellen). *Patient 9 had, in addition to optic atrophy, corneal band keratopathy in the left eye and vitreomacular traction in both eyes but was not treated operatively because potential visual gain was expected to be insignificant.
Fig. 2
Fig. 2
OCT features of autosomal dominant WFS1-associated optic neuropathy (AD WFS1-OA) and dominant optic atrophy (DOA). A. Lamination of the outer plexiform layer (blue arrows) in an AD WFS1-OA case. B. Comparison of peripapillary retinal nerve fiber layer thickness in healthy controls, DOA and AD WFS1-OA patients. Compared to DOA patients, thinning of retinal fiber nerve layer (RNFL) was more severe in AD WFS1-OD patients in all quadrants, with the exception of the temporal quadrant. C. Two examples of typical peripapillary RNFL patterns in patients with AD WFS1-OA and DOA.
See this image and copyright information in PMC

References

    1. Inoue, H. et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat. Genet.20, 143–148. 10.1038/2441 (1998). - PubMed
    1. Strom, T. M. et al. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum. Mol. Genet.7, 2021–2028. 10.1093/hmg/7.13.2021 (1998). - PubMed
    1. Eiberg, H. et al. Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. J. Med. Genet.43, 435–440. 10.1136/jmg.2005.034892 (2006). - PMC - PubMed
    1. deMuijnck, C., Brink, J. B., Bergen, A. A., Boon, C. J. F. & vanGenderen, M. M. Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum. Surv. Ophthalmol.68, 641–654. 10.1016/j.survophthal.2023.01.012 (2023). - PubMed
    1. Grenier, J. et al. WFS1 in optic neuropathies: Mutation findings in nonsyndromic optic atrophy and assessment of clinical severity. Ophthalmology123, 1989–1998. 10.1016/j.ophtha.2016.05.036 (2016). - PubMed

Publication types

Grants and funding

LinkOut - more resources