CERKL mutation causing retinitis pigmentosa(RP) in Indian population - a genotype and phenotype correlation study

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Mutations in the Ceroid-like protein (CERKL) gene are associated with Retinitis Pigmentosa (RP), a group of inherited retinal disorders.
• The clinical presentation of CERKL-related RP is often distinct from other RP phenotypes.
• This study focuses on the Indian population, investigating the prevalence and characteristics of CERKL mutations in RP patients.

Purpose of the Study:

• To identify patients with CERKL gene mutations within a cohort of Indian Retinitis Pigmentosa patients.
• To establish a genotype-phenotype correlation for CERKL mutations in this population.
• To characterize the specific clinical features associated with CERKL mutations in Indian RP patients.

Main Methods:

• Retrospective analysis of clinical data and ocular imaging from 14 unrelated RP patients with identified CERKL mutations.
• Next-generation sequencing (NGS) for variant detection, validated by Sanger sequencing.
• Collection of clinical data including fundus photography, autofluorescence, Optical Coherence Tomography (OCT), and Electroretinography (ERG).

Main Results:

• Three CERKL variants were identified: c.1045_1046delAT, c.847 C > T, and a novel c.899-1G>A.
• Characteristic retinal findings included bilateral symmetrical mild-to-moderate disc pallor, arteriolar attenuation, and sparse peripheral pigmentation (paucipigmentary RP).
• Early macular involvement with central hypo-autofluorescence and peripheral chorioretinal atrophy were observed, particularly in older patients.

Conclusions:

• CERKL gene mutations result in a clinically recognizable and distinct phenotype of Retinitis Pigmentosa.
• Understanding the genotype-phenotype correlation aids in identifying CERKL-related RP, predicting disease progression, and selecting patients for future gene therapies.