CDH23-associated Usher syndrome: genotype-phenotype correlations

Area of Science:

• Ophthalmology
• Genetics
• Retinal Degeneration

Background:

• Usher syndrome type 1D (USH1D) is a genetic disorder characterized by hearing loss and retinitis pigmentosa.
• Mutations in the CDH23 gene are a common cause of USH1D.
• Genotype-phenotype correlations are crucial for understanding disease progression and potential therapeutic targets.

Purpose of the Study:

• To investigate genotype-phenotype correlations in patients with CDH23-associated USH1D.
• To compare retinal imaging parameters based on the type of CDH23 variants (loss-of-function vs. non-loss-of-function).

Main Methods:

• Retrospective review of clinical notes and retinal imaging (fundus autofluorescence, optical coherence tomography).
• Classification of subjects into three groups based on CDH23 variant combinations: two loss-of-function (G1), one loss-of-function/one non-loss-of-function (G2), and two non-loss-of-function (G3).
• Comparison of age of onset, best-corrected visual acuity (BCVA), ellipsoid zone width (EZW), and outer nuclear layer (ONL) thickness.

Main Results:

• No statistically significant differences in age of onset (p=0.19) or BCVA (p=0.1) were observed between groups.
• Only one patient in the G3 group (non-loss-of-function variants) showed EZW loss.
• No significant differences in baseline or final ONL thickness (p=0.84) or the rate of ONL thinning (p=0.66) were found between groups.

Conclusions:

• While a trend towards a milder phenotype was suggested in patients with at least one non-loss-of-function CDH23 variant, statistical significance was not reached for the assessed parameters.
• Further research with larger cohorts may be needed to confirm these genotype-phenotype correlations in CDH23-associated USH1D.