Neoteric unreported variants in CERKL gene causing retinitis pigmentosa

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A 15-year-old female presented with diminution of vision in both eyes (BE), more at night, since 1 year. There was no history of trauma, ocular treatment, or similar complaints in her family. There was history of consanguineous marriage. Her best corrected visual acuity was 6/36, N6 in the right eye (RE) and 6/18, N6 in the left eye (LE). She was unable to read any of the pseudoisochromatic Ishihara plates. Rest of the anterior segment findings and intraocular pressures in BE were within normal limits. Fundus examination revealed pale disc, arteriolar attenuation, irregular pigmentary changes at the posterior pole, minimal bony spicules, peripapillary atrophy, and tessellated fundus [Fig. 1a and b]. RE structural optical coherence tomography showed loss of foveal contour with loss of outer nuclear layer in the subfoveal and perifoveal regions. LE showed foveal thinning with loss of photoreceptor layer [Fig. 1e and f]. Fundus autofluorescence showed hypoautofluorescent nasal half of the retina with incomplete ring of hypoautofluorescence surrounded by hyperautofluorescence at the fovea in BE [Fig. 1c and d]. Full-field electroretinogram showed flat wave in BE [Fig. 2], compared to normal electroretinogram of a healthy young child [Fig. 3]. Genetic testing for the patient showed homozygous novel variant (c.1094C > A) in CERKL gene in exon 8, which has pathogenic significance, causing premature truncation of protein resulting in increased oxidative stress, thereby causing degeneration of photoreceptors. The age of presentation of retinitis pigmentosa (RP) is around third decade.[1] Patients with CERKL mutation are known to present early with increased macular involvement and have pauci-pigmented fundus.[2] As per ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/?term=CERKL[gene]), there are 236 variants of CERKL gene causing RP, which are pathogenic or likely pathogenic. The inheritance pattern and prognosis were explained to the family members of the patient. The patient was advised to undergo genetic testing, but did not undergo the same because of logistic reasons, which is a limitation of this study. To conclude, we report a case of RP with novel unreported mutations (c.1094C >A) in eastern India.[3]Figure 1: (a) Color fundus photo of RE showing arteriolar attenuation, disc pallor, and minimal bony spicules in a tessellated fundus. (b) Color fundus photo of LE showing arteriolar attenuation, disc pallor, and minimal bony spicules in a tessellated fundus. (c) Fundus autofluorescence of RE showing granular hypoautofluorescence nasal to the disc. An incomplete ring of hypoautofluorescence surrounded by hyperautofluorescence at the fovea was also seen. (d) Fundus autofluorescence of LE showing granular hypoautofluorescence nasal to the disc. An incomplete ring of hypofluorescence surrounded by hyperautofluorescence at the fovea was also seen. (e) Structural OCT of through the fovea shows loss of foveal contour with loss of outer nuclear layer in the subfoveal and perifoveal regions. (f) Structural OCT of LE through the fovea shows foveal thinning with loss of photoreceptor layer. LE = left eye, OCT = optical coherence tomography, RE = right eyeFigure 2: (a–j) Full-field electroretinogram of both eyes showing grossly attenuated waveforms of all standard International society for clinical electrophysiology of vision (ISCEV) waveformsFigure 3: (a–e) Full-field electroretinogram of a normal healthy young child according to the ISCEV standardsDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.