Genetic dissection of non-syndromic retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) belongs to a group of pigmentary retinopathies. It is the most common form of inherited retinal dystrophy, characterized by progressive degradation of photoreceptors that leads to nyctalopia, and ultimately, complete vision loss. RP is distinguished by the continuous retinal degeneration that progresses from the mid-periphery to the central and peripheral retina. RP was first described and named by Franciscus Cornelius Donders in the year 1857. It is one of the leading causes of bilateral blindness in adults, with an incidence of 1 in 3000 people worldwide. In this review, we are going to focus on the genetic heterogeneity of this disease, which is provided by various inheritance patterns, numerosity of variations and inter-/intra-familial variations based upon penetrance and expressivity. Although over 90 genes have been identified in RP patients, the genetic cause of approximately 50% of RP cases remains unknown. Heterogeneity of RP makes it an extremely complicated ocular impairment. It is so complicated that it is known as “fever of unknown origin”. For prognosis and proper management of the disease, it is necessary to understand its genetic heterogeneity so that each phenotype related to the various genetic variations could be treated.

A Novel Copy Number Variation in PRPF31 Causes Dominant Rod-Cone Dystrophy By Haploinsufficiency

“…These results indicate that the mutant transcript was unstable and may be subjected to the nonsense-mediated decay mechanism. Haploinsu ciency in PRPF31 is a well-established mechanism in the pathogenesis of RCD [20], [21] , [22]. The majority of PRPF31 mutations result in null alleles, leading to haploinsu ciency and subsequent photoreceptor death in the retina [20], [21].…”

“…Haploinsu ciency in PRPF31 is a well-established mechanism in the pathogenesis of RCD [20], [21] , [22]. The majority of PRPF31 mutations result in null alleles, leading to haploinsu ciency and subsequent photoreceptor death in the retina [20], [21]. This mechanism is responsible for the incomplete penetrance of the disease phenotypes associated with PRPF31 variations [20].…”

Breaking genetic shackles: The advance of base editing in genetic disorder treatment

“…Initially manifesting as night blindness, RP gradually progresses to a more severe loss of vision, ultimately resulting in total blindness ( Hartong et al, 2006 ). To date, over 100 genes have been identified in various subtypes of RP with different genetic patterns, including the rhodopsin gene ( RHO ), the pre-mRNA processing factor 31 gene ( PRPF31 ), and the peripherin 2 gene ( PRPH2 ), among others ( Bhardwaj et al, 2022 ; Qin et al, 2023b ). Although Luxturna offers a treatment option for a minority of RP patients carrying RPE65 mutations, the genetic diversity of RP means that a universal cure for all patients is currently lacking ( Cross et al, 2022 ).…”

Posterior Polar Annular Choroidal Dystrophy: Genetic Insights and Differential Diagnosis in Inherited Retinal Diseases

“…Notably, most genetic variations associated with RP impact the rod photoreceptors, which are probably also the primary cells affected in PPACD. The genetic variants leading to photoreceptor degeneration merit further investigation in the context of PPACD to enhance our understanding and approach to this condition [57,60].…”