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

To evaluate the prevalence of achromatopsia (ACHM) associated with variants of RPGRIP1 , especially c.2710+374_2895+78del ( RPGRIP1 -ex18-DEL), and to confirm that these phenotypes were consistent with ACHM in Japanese patients.

This retrospective observational study involved a review of medical records from 52 patients across 47 Japanese families; all clinically diagnosed with ACHM.

Causative variants for ACHM were identified in 39 families through whole-exome sequencing, whole-genome sequencing, or polymerase chain reaction: PDE6C (13 families), RPGRIP1 -ex18-DEL (11 families), CNGA3 (11 families), CNGB3 (2 families), and GNAT2 (2 families). Patients with ACHM associated with RPGRIP1 -ex18-DEL variants did not exhibit significant difference in phenotype, including spherical equivalent refractive error, best-corrected visual acuity (BCVA), fundus appearance, ellipsoid zone grading of optical coherence tomography, and fundus autofluorescence pattern, compared with those with variants in CNGA3 or PDE6C at baseline (all, P > 0.05). For five patients with ACHM with RPGRIP1 -ex18-DEL variants, no change in BCVA or ellipsoid zone grading was noted over a follow-up period of >10 years (all, P > 0.05).

Variants in RPGRIP1 -ex18-DEL are unique hotspots with a high prevalence among Japanese patients with ACHM. Clinical findings in these patients are consistent with those in patients with ACHM from other causative genes.