Phenotypic Features of Patients With NR2E3 Mutations

Abstract

To describe the phenotypes of 5 patients with NR2E3 mutations. Methods: Two patients with familial and 3 with sporadic early-onset nyctalopia and retinal pigment abnormalities were screened for mutations in the NR2E3 gene (OMIM 604485). The clinical course, fundus features, visual field test results, and fluorescein angiographic and electrophysiologic findings were compared. Results: Three different mutations in NR2E3 were identified: R311Q and 2 novel mutations-missense change Q350R and an in-frame deletion of phenylalanine at position 71 (delF71) in exon 2. Three patients who were homozygous for R311Q had posterior subcapsular cataracts and a concentric ring of round pigment clumps. Electroretinograms were extinguished. A fourth patient, a 24-year-old man who was heterozygotic for R311Q and Q350R, had Goldmann-Favre syndrome. A fifth patient, a 10-year-old boy with heterozygotic mutations R311Q and delF71, had diminished foveal reflexes and subtle pigmentary changes, perhaps a forme fruste of Goldmann-Favre syndrome. Both of these patients had an identical spectral electroretinographic pattern characteristic of enhanced Scone syndrome. Conclusions: Molecular genetic testing is essential for establishing the correct diagnosis in patients with NR2E3 mutations because of the variable phenotype associated with these degenerations. Two novel NR2E3 mutations are described that are associated with Goldmann-Favre syndrome and enhanced Scone syndrome.

Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults

“…A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28]. The fundus of patient 3 was extensively scarred and marked with white spots, as seen in the IR and SD-OCT images.…”

“…Patient 3 showed R311Q homozygosity, which is a common cause of ESCS [28]. A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28].…”

Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults

“…A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28]. The fundus of patient 3 was extensively scarred and marked with white spots, as seen in the IR and SD-OCT images.…”

“…Patient 3 showed R311Q homozygosity, which is a common cause of ESCS [28]. A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28].…”

Novel Pathogenic Sequence Variants in NR2E3 and Clinical Findings in Three Patients

“…The previously reported mutations were as follows: c.226C > T, p.(R76W), was seen in patient I; c.119-2A > C was seen as homozygous in patient II and heterozygous in patient III ( Table 1). All three patients showed signs of pigment clumping that extended in a band from the vascular arcades to the mid-periphery with a characteristic corresponding band of a decreased signal in AF extending from the vascular arcades to the mid periphery, which is consistent with the literature regarding patients with recessive NR2E3 mutations [3,8,19,35,[38][39][40][41]. An increased macular AF signal was also noted.…”

Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease

“…Autosomal recessive NR2E3-related disease manifests as a slow disease progression in ESCS patients, with good visual acuity preservation in the vast majority of cases, good overall macular function preservation, good retention of far peripheral vision, and relatively slow progression of kinetic visual field loss as noted by previous studies [22,31,32,60,61], which is consistent with what we observed in our patients. A retrospective literature analysis on the clinical characteristics of the Nr2e3 patients shows a gradual decline of the visual acuity and reduced ERG over time (Table S1) [24,27,28,35,38,41,59,60,. This pattern of progression is similar to the observations of rd7 mice.…”

Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults

“…A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28]. The fundus of patient 3 was extensively scarred and marked with white spots, as seen in the IR and SD-OCT images.…”

“…Patient 3 showed R311Q homozygosity, which is a common cause of ESCS [28]. A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28].…”

Novel Pathogenic Sequence Variants in NR2E3 and Clinical Findings in Three Patients

“…The previously reported mutations were as follows: c.226C > T, p.(R76W), was seen in patient I; c.119-2A > C was seen as homozygous in patient II and heterozygous in patient III ( Table 1). All three patients showed signs of pigment clumping that extended in a band from the vascular arcades to the mid-periphery with a characteristic corresponding band of a decreased signal in AF extending from the vascular arcades to the mid periphery, which is consistent with the literature regarding patients with recessive NR2E3 mutations [3,8,19,35,[38][39][40][41]. An increased macular AF signal was also noted.…”

Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease

“…Autosomal recessive NR2E3-related disease manifests as a slow disease progression in ESCS patients, with good visual acuity preservation in the vast majority of cases, good overall macular function preservation, good retention of far peripheral vision, and relatively slow progression of kinetic visual field loss as noted by previous studies [22,31,32,60,61], which is consistent with what we observed in our patients. A retrospective literature analysis on the clinical characteristics of the Nr2e3 patients shows a gradual decline of the visual acuity and reduced ERG over time (Table S1) [24,27,28,35,38,41,59,60,. This pattern of progression is similar to the observations of rd7 mice.…”

Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults

“…A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28]. The fundus of patient 3 was extensively scarred and marked with white spots, as seen in the IR and SD-OCT images.…”

“…Patient 3 showed R311Q homozygosity, which is a common cause of ESCS [28]. A prospective study by Pachydaki et al documented phenotypic characteristics of several R311Q cases, including round, pigmented clumping along the retinal mid-periphery, which is consistent with our findings [28].…”

Novel Pathogenic Sequence Variants in NR2E3 and Clinical Findings in Three Patients

“…The previously reported mutations were as follows: c.226C > T, p.(R76W), was seen in patient I; c.119-2A > C was seen as homozygous in patient II and heterozygous in patient III ( Table 1). All three patients showed signs of pigment clumping that extended in a band from the vascular arcades to the mid-periphery with a characteristic corresponding band of a decreased signal in AF extending from the vascular arcades to the mid periphery, which is consistent with the literature regarding patients with recessive NR2E3 mutations [3,8,19,35,[38][39][40][41]. An increased macular AF signal was also noted.…”

Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease

“…Autosomal recessive NR2E3-related disease manifests as a slow disease progression in ESCS patients, with good visual acuity preservation in the vast majority of cases, good overall macular function preservation, good retention of far peripheral vision, and relatively slow progression of kinetic visual field loss as noted by previous studies [22,31,32,60,61], which is consistent with what we observed in our patients. A retrospective literature analysis on the clinical characteristics of the Nr2e3 patients shows a gradual decline of the visual acuity and reduced ERG over time (Table S1) [24,27,28,35,38,41,59,60,. This pattern of progression is similar to the observations of rd7 mice.…”