%0 Journal Article
%T Detailed phenotype and long-term follow-up of RAB28-associated cone-rod dystrophy.
%A Rao NT
%A Sumaroka A
%A Santos AJ
%A Parchinski KM
%A Weber ML
%A Maguire AM
%A Cideciyan AV
%A Aleman TS
%J Ophthalmic Genet
%V 0
%N 0
%D 2024 Jul 2
%M 38956823
%F 1.274
%R 10.1080/13816810.2024.2362204
%X <B>UNASSIGNED: </B>To gain an insight into the pathophysiology of RAB28-associated inherited retinal degeneration through detailed phenotyping and long-term longitudinal follow-up.<BR><B>UNASSIGNED: </B>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).<BR><B>UNASSIGNED: </B>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 μm) expansion over a six-year period.<BR><B>UNASSIGNED: </B>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.