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The largest molecular study of RP in Italy has reported 591 probands with family history and sporadic cases.

Researchers at the Department of Ophthalmology, at the University of Milan, have published the largest molecular study of Italian patients with RP in the literature.  The research recruited a total of 591 probands over an 8-year period showing that there were 315 patients with a family history (53.3%) and 276 sporadic cases (46.7%).  While the research community knows that there is no definitive treatment available to date, there are huge strides for the development of several gene-targeted treatments.  In addition, the collation of data is critical to manage RP assessment, genetic counselling, and building valuable recruitment cohorts in preparation for pending clinical studies.


As of today’s date, inherited retinal degenerations (IRDs) have identified 271 genes causing retinal disease, comprising >12,000 mutations catalogued in the literature.  IRDs include Retinitis Pigmentosa (RP), Leber congenital amaurosis (LCA), cone/cone-rod dystrophy (CD/CRD), congenital stationary night blindness (CSNB), and the syndromic ciliopathies of Alström syndrome, Bardet-Biedl syndrome (BBS), Joubert syndrome (JBS) and Usher syndrome (US).  RP is genetically heterogeneous and may be transmitted by autosomal dominant (AD), autosomal recessive, (AR), X-linked (XL), di-genic, polygenic and mitochondrial patterns of inheritance.  RP has a typical worldwide prevalence of 1/4,000, ranging from 1.7/10,000 to 3.3/10,000 in European studies, while there are higher frequencies of RP in southern and central India, northern China and the United States Navajo Indians.  As commented by the researchers in their study, “the clinical implications of achieving molecular confirmation of RP are multi-fold. As phenotypic differentiation with respect to other partially overlapping hereditary retinal dystrophies can be difficult in specific circumstances, molecular testing may help classification and prognosis in cases with known genotype-phenotype correlations. Molecular confirmation of the inheritance pattern is also crucial for appropriate genetic counselling and identification of carrier or pre/oligosymptomatic relatives”.


The current research collected both clinical and genetic data from the 591 probands and compared differences between presumed inheritance based on observation, and a diagnostic yield of cases with family history and the prevalence of RP inheritance patterns.  The results of the study showed a mean diagnostic yield of molecular testing among patients with a family history of retinal disorders of 55.2%, and sporadic cases among patients of 37.4%. For this Italian cohort, the average age of onset of the different classes of RP were autosomal dominant RP, 19.3 ± 12.6 years; autosomal recessive RP, 23.2 ± 16.6 years; X-linked RP, 13.9 ± 9.9 years and Usher syndrome, 18.9 ± 9.5 years.  Slight differences of proportions for the inheritance differences, compared against comparable data in the international literature, are likely due to differences in the context of genetic background, patient selection bias (assessing severe cases), or heterogeneity in clinical information but the overall picture was consistent to other international studies.  A summary of the breakdown showed that AD-RP had 10% of the cohort, AR-RP for 16%, XL-RP for 4%, Usher for 7%, and unsolved were reported for 63% of the cases.  In conclusion of their study, researchers commented that “it is only a matter of time before new gene therapies become available. Genetically solved patients will have the advantage of being quickly eligible for clinical trials or access to pharmacologic treatment”.