Novel causative variants in patients with achromatopsia

To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM).

Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS).

Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence.

These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.