High-Throughput Sequencing to Identify Mutations Associated with Retinal Dystrophies.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Retinal dystrophies (RD) are a group of over 270 genetic disorders affecting millions globally.
• Understanding the genetic basis of RD is crucial for developing effective treatments.

Purpose of the Study:

• To establish a whole exome sequencing (WES) pipeline for rapid identification of disease-causing mutations in RD patients.
• To analyze sequence variants and their clinical relevance in a cohort of 26 unrelated RD patients.

Main Methods:

• Whole exome sequencing (WES) was employed to detect genetic variants.
• Sanger sequencing was used for deep-intronic variant identification and co-segregation analysis.
• Ophthalmic examinations and genetic analysis were performed on all patients.

Main Results:

• Identified 37 sequence variants in 17 genes, including nine novel disease-associated variants.
• Classified variants: 21 pathogenic, 4 benign/likely benign, and 12 of uncertain significance.
• Discovered deep-intronic variants in the *ABCA4* gene in two Stargardt disease cases.

Conclusions:

• WES-based mutation analysis is vital for clinical decisions, genetic diagnosis, and counseling in RD.
• Expanding the mutation spectrum and understanding genotype-phenotype correlations are essential for genetic therapies.
• This study supports the utility of WES in unraveling the genetic complexity of retinal dystrophies.