DELETION INVOLVING EXON 18 OF RPGRIP1 IS a MAJOR CAUSE OF ACHROMATOPSIA.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Achromatopsia (ACHM) is a rare inherited retinal disorder.
• Genetic variations are the primary cause of ACHM.
• Understanding gene prevalence and associated phenotypes is crucial for diagnosis and management.

Purpose of the Study:

• To determine the prevalence of achromatopsia (ACHM) linked to RPGRIP1 gene variants, particularly c.2710+374_2895+78del (RPGRIP1-ex18-DEL), in Japanese patients.
• To confirm that the clinical presentation of ACHM in these patients aligns with established phenotypes.

Main Methods:

• Retrospective review of medical records from 52 patients across 47 Japanese families diagnosed with ACHM.
• Genetic analysis using whole-exome sequencing, whole-genome sequencing, and polymerase chain reaction to identify causative variants.
• Phenotypic evaluation including visual acuity, refractive error, and retinal imaging.

Main Results:

• RPGRIP1-ex18-DEL variants were identified as causative in 11 out of 39 families with ACHM.
• No significant phenotypic differences were observed in patients with RPGRIP1-ex18-DEL variants compared to those with PDE6C or CNGA3 variants.
• Long-term follow-up (>10 years) of five patients with RPGRIP1-ex18-DEL variants showed stable visual acuity and retinal structure.

Conclusions:

• RPGRIP1-ex18-DEL variants represent a significant genetic hotspot for achromatopsia in the Japanese population.
• The clinical characteristics of ACHM associated with RPGRIP1-ex18-DEL are consistent with ACHM caused by other known genes.
• This study reinforces the importance of RPGRIP1 gene analysis in diagnosing achromatopsia.