An Italian research team report on a pericentral retinitis pigmentosa study identifying several genetic variants

Italian researchers at the Università degli Studi della Campania, Naples, have reported the results of the first study from a European cohort of pericentral RP patients.  A total of 54 subjects from 48 independent families with pericentral RP, non-syndromic and syndromic, were evaluated through a full ophthalmological examination, including clinical exomic or retinopathy gene panel sequencing. Disease-causative variants were identified in 22 of the 35 families (63%) in 10 different genes, four of which are also responsible for syndromic RP. In addition, thirteen of the 34 likely pathogenic variants were novel, indicating that the study confirms the mild phenotype of pericentral RP, extending the spectrum of genes associated with the disease.

 

After reviewing the genetic analysis among 39 patients (from 35 unrelated families), causative mutations were found in 22 out of 35 analysed families (63% diagnostic rate). Pathogenic or likely pathogenic variants were identified in the following several genes, including: USH2A in 9 families, CEP290 in 2 families, RP1 in 2 families, PRPF31 in 2 families, PDE6B in 2 families, while BBS2, NR2E3, PEX1, PRPH2 and RHO were in 1 family.  According to the data, USH2A was the most frequently mutated gene in the cohort, accounting for over one third of the cases analysed (9 out of the 25 solved familial cases). Eight patients (7 families) harbouring mutations in USH2A displayed pericentral RP in the context of an Usher syndrome type II, while two patients with causative variants in USH2A showed a normal audio-vestibular response. Interestingly, almost two thirds of the solved cases of pericentral RP (i.e. 14 out of 22) harboured putatively pathogenic mutations in genes involved in ciliary development and function, such as BBS2 (one case), CEP290 (two cases), RP1 (two cases) and USH2A (nine cases).

 

Commenting on the report, the researchers stated “our study, carried out for the first time on patients of European origin, adds important insights into the clinical presentation and genetic defects of pericentral RP. Interestingly, it expands the number of genes associated with the pericentral RP phenotype, including those involved in Usher and other syndromic conditions.  Consequently, the finding may suggest that, “whenever a pericentral RP is diagnosed, it is important to perform audio-vestibular examination, even in the absence of hearing symptoms”.  The clinical characterization of the cohort confirms a mild phenotype of pericentral RP, particularly in terms of BCVA, visual field and ERG responses.

294 thoughts on “An Italian research team report on a pericentral retinitis pigmentosa study identifying several genetic variants”

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