SSBP1 mutations in dominant optic atrophy with variable retinal degeneration.

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Autosomal dominant optic atrophy (ADOA) causes early childhood vision loss.
• OPA1 mutations are common, but some ADOA cases lack identified genetic causes.

Purpose of the Study:

• Identify novel genes associated with ADOA.
• Investigate the causality of these genes in ADOA pathogenesis.

Main Methods:

• Performed linkage analysis and sequencing in families and individuals with ADOA.
• Conducted in silico and in vivo (zebrafish model) functional studies.

Main Results:

• Identified three missense variants in the SSBP1 gene linked to ADOA.
• Demonstrated that SSBP1 variants impair single-strand DNA binding and retinal ganglion cell development in zebrafish.
• Established a new ADOA locus on chromosome 7q33-q35.

Conclusions:

• Pathogenic variants in SSBP1 cause ADOA and variable retinal degeneration.
• SSBP1 plays a crucial role in retinal development and function.