A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family.

Abstract

Background: Cone dystrophy is a heterogeneous hereditary retinal disorder with disease symptoms appearing in the late first or early second decades of life.

Methods: A consanguineous Pakistani family with three affected individuals underwent detailed clinical and genetic investigation.

Results: The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia. Fundus images showed bilateral peripapillary atrophy, bilateral dull foveal reflex, tilted disc, tessellated fundus, and hyperfluorescence at the peripheral superior temporal arcade and leak at an early stage. OCT macula and angiography findings suggested traction near the disc in the right eye and sub-retinal fluid at the fovea in the left eye. Retinal layers were normal toward the periphery but disorganized near the disc. Full visual field tests showed bilateral central scotoma, while single visual field tests indicated bilateral generalized depression of the visual field. The proband showed normal bilateral intraocular pressure, normal choroidal vessels, and unremarkable anterior segment. Exome sequencing identified a novel homozygous missense variant (POC1B:NM_172240.3:c.1391T>C;p.L464P) in the proband. Existing evidence supported pathogenicity of the identified variant in the family.

Conclusion: In conclusion, we document a first-ever Pakistani family with POC1B-related cone dystrophy.