TULP1 related retinal dystrophy: report of rare and novel variants with a previously undescribed phenotype in two cases.

PURPOSE: To report on two rare and one novel TULP1 pathogenic variants in two patients associated with a previously uncharacterized phenotype of retinal degeneration. METHODS: Case report. RESULTS: A 4 year-old and a 19 year-old female presented with reduced vision and bilateral bull's eye maculopathy. In both patients, a unique pattern of perivascular retinal degeneration was noted. Electroretinography was consistent with a cone-rod dystrophy. Sequence analysis identified pathogenic variants in the TULP1 gene c.1087 G > A, p.(Gly363Arg); c.1568 G > A, p.(Cys523Tyr); and c.821delA, p.(Lys274ArgfsTer36). CONCLUSION: Patients with TULP1-related retinal dystrophy can have a distinctive retinopathy with a unique pattern of macular degeneration and periarteriolar vascular pigmentation.

Clinical characteristics of recessive retinal degeneration due to mutations in the CDHR1 gene and a review of the literature.

BACKGROUND: The clinical phenotype of patients presenting with autosomal recessive CDHR1-related retinopathy has not been well described. MATERIALS AND METHODS: This is a retrospective case series of patients presenting to a single institution. Clinical data, including age, visual acuity, dilated fundus exam, fundus photos, fundus autofluorescence (FAF), optical coherence tomography, full-field electroretinograms (ERGs), and results of genetic testing, were collected. RESULTS: Four patients were identified to have biallelic mutations in the CDHR1 gene. All four patients were found to have at least one c.783G>A (p.Pro261 = ) mutation. A novel splice site mutation, c.152-2A>G, was identified in two patients. Patients became symptomatic between the fourth and sixth decades of life. Three patients presented initially with nyctalopia and peripheral visual field constriction, and one patient presented with simultaneous onset of photophobia and nyctalopia. The fundus appearance was characterized by macular atrophy with or without peripheral retinal pigment epithelium changes and arteriolar attenuation. FAF showed a hyperautofluorescent ring surrounding a central area of speckled hypoautofluorescence. Full-field electroretinography was available on three patients and showed decreased cone-and-rod responses. CONCLUSIONS: CDHR1-related retinal dystrophy should be considered in adult patients with a retinal dystrophy who present with symptoms of cone-and-rod dysfunction and macular atrophy on ophthalmoscopic examination.