Clinical and Molecular Characterization ofPROM1-Related Retinal Degeneration

Abstract

Key Points Question What are the clinical and molecular characteristics of PROM1- related retinal degeneration? Findings In this case series of 19 patients with PROM1 -related retinal degeneration, recessive variants were associated with early-onset, severe panretinal degeneration, whereas the dominant disease was associated with the c.1117C>T variant and a late-onset, milder phenotype that predominantly involves the macula. In addition, the dominant variant was preferentially associated with cone photoreceptors. Meaning A better understanding of the clinical and molecular characteristics of PROM1- related retinal degeneration may aid development of future treatments, including gene therapy and optogenetics.

Monitoring progression of retinitis pigmentosa: current recommendations and recent advances

“…Thus, the dominant cases associated with a specific missense variant (c.1117C>T) show milder, cone-driven phenotype, suggesting that the dominant disease is preferentially associated with cone photoreceptors. [94] The M-and L-cone opsin genes situated on the long arm of the X chromosome are another example of highly variable severity of the phenotype, which can vary from mild colour deficiency to blue cone monochromacy (BCM) depending on the variant. [95] USH2A is a large gene located on chromosome 1 that causes about 30% of all Usher type 2 cases, but also about 20% of autosomal recessive RP.…”

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

“…This group includes several proteins that play a role in eye morphogenesis in Drosophila and humans ( Jukam and Desplan, 2011 ; Mahato et al, 2018 ; Marrone et al, 2011a ; Ray et al, 2020 ). Moreover, these factors are not only associated with various ocular dystrophies but also involved in cancer development and regulation of stem cell maintenance and differentiation, cell growth, and metabolism ( Cehajic-Kapetanovic et al, 2019 ; Collison et al, 2019 ; Jamal et al, 2020 ; Lu et al, 2019 ; Priedigkeit et al, 2021 ; Wu et al, 2020 ). For example, in Drosophila, prominin (Prom), a homolog of human CD133, maintains mitochondrial function, regulates body size and weight, and influences animal longevity by controlling insulin and TOR signaling ( Ryu et al, 2019 ; Wang et al, 2019 ; Zheng et al, 2019 ).…”

Childhood-onset genetic cone-rod photoreceptor diseases and underlying pathobiology

“…Mutations result in a variety of phenotypes including CORD and bull's-eye maculopathy [43] . Autosomal recessive truncating, splice site and missense variants were postulated to result in total loss of function and were associated with a more severe phenotype with an earlier age of onset and a retina-wide effect whereas patients with an autosomal dominant variant showed a less severe later onset phenotype with primarily macular involvement [41] .

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