A New Variant in the PRPF6 Gene Leading to Retinitis Pigmentosa: A Case Report.

We report on a case of a 34-year-old Hispanic female patient with a medical history of diabetes mellitus, thyroid disease, and cataract surgery in the right eye, who was evaluated due to progressive vision loss in both eyes. The patient had waxy pallor of the optic disc, vessel attenuation, retinal pigment epithelium (RPE) degeneration, and bony spicules OU. These findings are compatible with a diagnosis of retinitis pigmentosa (RP). Gene sequencing and deletion/duplication analysis were performed. The patient was positive for a heterozygous mutation in the PRPF6 gene with the variant c.2228C>T (p.Thr743Ile). This PRPF6 variant was reported as a variant of unknown significance. The Combined Annotation Dependent Depletion (CADD) score of this PRPF6 variant is 23.5, which strengthens the idea that it could potentially be associated with RP. To our knowledge, this is the first case reported on an RP patient with the PRPF6 variant c.2228C>T (p.Thr743Ile). Our case suggests that this PRPF6 variant may be associated with bilateral RP. Further molecular studies are warranted to better understand the molecular changes in the PRPF6 gene leading to RP.

Pseudodominant Inheritance of Retinitis Pigmentosa Due to Mutations in the Phosphodiesterase 6B Gene: A Case Report.

Mutations in the phosphodiesterase 6B (PDE6B) gene are a rare cause of autosomal recessive retinitis pigmentosa (arRP). We report on a non-consanguineous family with a pseudodominant inheritance of RP due to PDE6B mutations. We conducted a chart review of four members of a Puerto Rican family who underwent a comprehensive ophthalmic evaluation by at least one of the authors. The mutational screening was done using a genotyping microarray provided by Invitae Corporation, using next-generation sequencing (NGS) technology. Genomic DNA obtained from saliva samples is enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. A descriptive analysis was done. Patient 1A had a normal ophthalmic examination and a heterozygous pathogenic variant in the PDE6B gene c.1540del PLeu514Trpfs*61. Patients 1B, 2A, and 2B had mid-peripheral retinitis pigmentosa, concentric visual field ring scotomata in both eyes (OU), extinguished electroretinogram (ERG), and homozygous pathogenic variants in the PDE6B gene c.1540del PLeu514Trpfs*61. Even though mutations in the PDE6B gene usually lead to arRP, they may be inherited in a pseudodominant pattern in geographically isolated populations. Genotyping studies in patients with RP are warranted to classify inheritance mode correctly.

Stargardt Disease Due to an Intronic Mutation in the ABCA4: A Case Report.

Purpose: To report on a patient with Stargardt disease (STGD1) and with an intronic mutation in the ABCA4 gene. Patients and Methods: A 69-year-old female patient presented to the clinic complaining of progressive vision loss. The ophthalmic evaluation was remarkable for a best corrected visual acuity of counting fingers at 5' in the right eye and 3' in the left eye. Imaging revealed deep extensive atrophy of the central macula, epithelial pigment hyperplasia, and other areas of multifocal atrophy in the right eye. Furthermore, fundus autofluorescence imaging of the macula showed central hypoautofluorescence with bilateral expansion to the periphery in both eyes. A full-field electroretinogram showed a normal rod response, with decreased cone response, bilaterally. Genetic testing was positive for a homozygous intronic mutation in the ABCA4 gene of the variant c.5714+5G>A. Conclusions and Importance: Patients with STGD1 due to presumed mild or moderate mutations in the ABCA4 gene may have a more severe presentation and progression of the disease. Based on this, the first report of a genotype-phenotype correlation in a Puerto Rican patient with STGD1 disease, genotyping all Puerto Rican patients is warranted.

Retinitis Pigmentosa in the Puerto Rican Population: A Geographic Distribution.

Background: Previous studies have reported on retinitis pigmentosa (RP) in Puerto Rico. Information on the geographic distribution of RP mutations in Puerto Rico may lead to higher rates of diagnosis and co-management. We aimed to evaluate whether there are areas with increased incidence of genes leading to RP in the Island. Materials and Methods: We conducted a non-concurrent prospective study on the genotype of 241 patients with RP in Puerto Rico. We evaluated their townships to determine whether there are clusters of genes leading to RP. Genetic studies were done using the Invitae inherited retinal diseases panel analyzing 330 genes. Results: A total of 100 patients were evaluated. Clusters of patients with mutations were found in certain townships. As depicted in the map, a cluster of patients with a mutation in the PDE6B gene was found in San Juan (9), those with the BBS1 gene occurred in San Juan (6) and Bayamón (4), mutations on the USH2A gene were found in Toa Baja (5), mutations in the CRB1 gene appeared in Ciales (4), and mutations in the BBS7 were found in Aibonito (2). Other mutations are scattered throughout the Island. Conclusion: Clusters of mutations were identified in several townships including San Juan, Bayamón, Toa Baja, Ciales, and Aibonito. Some of these are isolated geographically. Additional mutations were identified but only the most pertinent were reported. Genetic studies are warranted in all patients with RP in Puerto Rico.

A Genotype-Phenotype Analysis of Usher Syndrome in Puerto Rico: A Case Series.

Introduction Patients with Usher syndrome (USH) have retinitis pigmentosa (RP) and hearing loss inherited as an autosomal recessive (ar) trait. Mutations in the USH2A gene are the most common cause of Usher syndrome. We report the genotype-phenotype correlation in 10 patients with Usher syndrome from Puerto Rico (PR). This is the first genotype-phenotype analysis of patients with the syndrome in PR. Methods We conducted a chart review of patients who carried an Usher syndrome diagnosis. They underwent a comprehensive ophthalmic evaluation by at least one of the authors. This included best corrected visual acuity (BCVA), visual field mean deviation (VF MD), pattern standard deviation (PSD), and macular optical coherence tomography (mOCT) average volume and thickness. Genotyping was done using the Invitae Inherited Retinal Disease (IRD) Panel. Results Three patients had a logMAR BCVA of 1.0 or worse. The median VF MD was -29.7 dB and -29.2 dB in the OD and OS, respectively. The median PSD was 5.5 dB and 5.7 dB in the OD and OS, respectively. Upon macular OCT, patients had a median volume of 8.4 µm3 and 8 µm3 in the OD and OS, respectively. The median thickness was 235 µm and 223 µm in the OD and OS, respectively. All patients had pathogenic USH2A variants, and eight of these were compound heterozygotes. The most common variants were p.Cys575Tyr and p.Glu767Serfs*21, each present in four patients. Patients with the p.Cys759Phe variant had the worst phenotype with the worst BCVA, largest VF MD, and slimmer macular thickness. Conclusion Our findings are compatible with previously reported pathogenic mutations in the USH2A gene. However, the p.Cys759Phe variant has previously been correlated with a mild phenotype. In our study, the p.Cys759Phe variant correlated with the most severe phenotype. This variant has a high prevalence in the Spanish population, and PR was a Spanish colony for 400 years. The presence of this variant could be traced back to Spain. Genotyping patients with Usher syndrome is of utmost importance. Further studies to evaluate the common founder effect of patients with the syndrome in PR are warranted.