Novel causative variants in patients with achromatopsia

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Achromatopsia (ACHM) is a rare, inherited retinal disorder characterized by reduced visual acuity, photophobia, and complete or partial absence of color vision.
• Genetic defects in genes such as CNGA3 and PDE6C are known causes of ACHM.
• Identifying novel genetic variants is crucial for understanding ACHM pathogenesis and developing targeted therapies.

Observation:

• This study investigated seven unrelated consanguineous families with ACHM.
• Multimodal retinal imaging and full-field electroretinography (ffERG) were performed on patients.
• Next-generation sequencing (NGS) was utilized for genetic analysis.

Findings:

• Three novel homozygous variants in CNGA3 (c.967G>C, c.101+1G>A, c.395+1G>T) and two novel homozygous variants in PDE6C (c.1899C>A, c.1072-1G>C) were identified.
• Mutation segregation was confirmed in three of the seven families.
• Patients exhibited nonrecordable ffERG 30-Hz flicker responses, diminished cone function, preserved rod function, and variable foveal abnormalities.

Implications:

• The identified novel variants expand the known spectrum of genetic causes for achromatopsia.
• This research provides valuable genotype information for ACHM patients.
• These findings may contribute to the development of future gene-specific therapies for achromatopsia.