Nonsyndromic Retinitis Pigmentosa With Pathogenic CEP290 Mutations.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• CEP290 gene variants are typically linked to Leber congenital amaurosis, causing severe early-onset vision loss.
• Nonsyndromic retinitis pigmentosa (RP) presents with progressive peripheral vision loss and night blindness.

Purpose of the Study:

• To report a unique case of RP with foveal sparing and preserved central vision in a patient with pathogenic CEP290 variants.
• To investigate the genetic basis and phenotypic spectrum of CEP290-associated retinal disorders.

Main Methods:

• Clinical examination of a 28-year-old woman with visual impairment.
• Comprehensive genetic testing, including whole exome sequencing, to identify causative mutations.
• Analysis of CEP290, BBS5, PDE6A, and RPGR gene variants.

Main Results:

• The patient presented with mild RP symptoms, including peripheral vision loss and nyctalopia, but maintained 20/25 visual acuity.
• Genetic analysis revealed two pathogenic nonsense mutations in CEP290 (c.1666del and c.4057G>T).
• Despite severe mutations in CEP290, the patient exhibited a mild, stable RP phenotype, suggesting potential genetic modifiers.

Conclusions:

• This case broadens the understanding of CEP290-related eye diseases, demonstrating a milder RP phenotype.
• The findings highlight the potential influence of genetic modifiers on the severity of CEP290-associated visual impairment.