Detailed phenotype and long-term follow-up of RAB28- associated cone-rod dystrophy
- PMID: 38956823
- DOI: 10.1080/13816810.2024.2362204
Detailed phenotype and long-term follow-up of RAB28- associated cone-rod dystrophy
Abstract
Purpose: To gain an insight into the pathophysiology of RAB28-associated inherited retinal degeneration through detailed phenotyping and long-term longitudinal follow-up.
Methods: The patient underwent complete ophthalmic examinations. Visual function was assessed with microperimetry, full-field electroretinography (ffERG), imaging with optical coherence tomography (OCT), short-wave (SW), and near-infrared (NIR) fundus autofluorescence (FAF).
Results: A healthy Haitian woman with homozygous pathogenic variants (c.68C > T; p.Ser23Phe) in RAB28 presented at 16 years of age with a four-year history of blurred vision. Visual acuities were 20/125 in each eye, which remained relatively stable since. At age 27, cone ffERGs were non-detectable and borderline for rod-mediated responses. Kinetic fields were full to a V-4e target, undetectable to a small I-4e stimulus. Microperimetry showed an absolute central scotoma surrounded by a pericentral relative scotoma. SD-OCT showed an undetectable or barely detectable foveal and parafoveal photoreceptor outer nuclear layer (ONL), photoreceptor outer segment (POS), and retinal pigment epithelium (RPE) signals and loss of the SW- and NIR-FAF signals. This atrophic region was separated from a normally laminated retina by a narrow transition zone (TZ) of hyper SW- and NIR-FAF that co-localized with preserved ONL but abnormally thinned POS and RPE. There was minimal centrifugal (<100 m) expansion over a six-year period.
Conclusion: The cone-rod dystrophy phenotype documented herein supports a critical role of RAB28 for cone function and POS maintenance. Severe central photoreceptor and RPE loss with a predilection for POS loss in TZs suggests possible disruptions of complex mechanisms that maintain central cone photoreceptor and RPE homeostasis.
Keywords: BBS; BBS7; Bardet-Biedl syndrome; OCT; Rab28; cone dystrophy; cone-rod dystrophy.
Similar articles
-
Bardet-Biedl syndrome-7 (BBS7) shows treatment potential and a cone-rod dystrophy phenotype that recapitulates the non-human primate model.Ophthalmic Genet. 2021 Jun;42(3):252-265. doi: 10.1080/13816810.2021.1888132. Epub 2021 Mar 17. Ophthalmic Genet. 2021. PMID: 33729075 Free PMC article.
-
Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.Ophthalmic Genet. 2016 Dec;37(4):445-452. doi: 10.3109/13816810.2015.1126616. Epub 2016 Mar 30. Ophthalmic Genet. 2016. PMID: 27028354 Free PMC article.
-
RDH12 Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function.Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5225-5236. doi: 10.1167/iovs.18-24708. Invest Ophthalmol Vis Sci. 2018. PMID: 30372751
-
Near-Infrared Autofluorescence: Early Detection of Retinal Pigment Epithelial Alterations in Inherited Retinal Dystrophies.J Clin Med. 2024 Nov 15;13(22):6886. doi: 10.3390/jcm13226886. J Clin Med. 2024. PMID: 39598030 Free PMC article. Review.
-
Progressive Cone Dystrophy and Cone-Rod Dystrophy.Adv Exp Med Biol. 2025;1467:61-67. doi: 10.1007/978-3-031-72230-1_12. Adv Exp Med Biol. 2025. PMID: 40736814 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous