Background: Retinitis pigmentosa (RP) is an inherited degenerative disease causing severe retinal dystrophy and visual impairment mainly with onset in infancy or adolescence.
RP is genetically heterogeneous and the identification of the underlying genetic cause has become particularly important in the era of novel therapeutic options such as gene therapy. The application of next generation sequencing (NGS) through targeted gene panels has become an efficient tool to encounter the enormous genetic heterogeneity of RP.
Methodology: we will perform a retrospective study, collecting and reviewing all the clinical and genetic data of patients affected by RP, followed in the Centre of Retinal Dystrophy of Policlinico Umberto I Hospital from 2008 to present. A genetic consultation and the possibility to have genetic tests will be offered to still genetically uncharacterized patients.
Aim: This multidisciplinary project, involving an ophthalmologist with relevant expertise in this filed and clinical geneticists, will permit to perform an accurate genotype-phenotype correlation for this large cohort of patients. The aim is to possibly disclose previously unknown correlations and to increase knowledge about its pathogenesis. This results will be also useful in the diagnostic iter of RP patients, to prevent possible complications and to offer them the new upcoming targeted therapeutic opportunities.
Genetic results, together with an accurate clinical and instrumental characterization of patients, has direct impact on planning targeted therapies and follow-up in the era of novel therapeutic options such as gene therapy and cell stem therapy[Jespersgaard et al., Sci Rep. 2019;9(1):1219; Strafella et al., Genes (Basel). 2019;10(10):792].
The field of retinal dystrophies is in fact one of the most advanced in terms of targeted therapy related to genetic dysfunction, and this retrospective study could be useful in order to propose to patients gene therapies and / or stem cells currently under study.
The application of NGS approaches in unresolved cases is also important to disclose previously unknown genetic diagnosis and to offer an appropriate genetic counseling calculating the recurrence risk of disease within the family.
A preliminary result of this group research has been recently published on BMC Ophtalmology, describing for the first time the association of the specific phenotype of Coats' angiomatosis to mutations in the RPGR gene in a family showing an X-linked dominant transmission pattern.