De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases

Area of Science:

• Ophthalmology
• Genetics
• Medical Genomics

Background:

• Inherited eye diseases (IEDs) represent a significant cause of visual impairment.
• Understanding the genetic basis of IEDs is crucial for diagnosis and treatment.
• Trio-based analysis provides a powerful approach to identify causative genetic variants.

Purpose of the Study:

• To describe genotype-phenotype associations in a trio-based cohort of inherited eye diseases.
• To gain novel insights into the genetic characteristics of IEDs in a Chinese population.
• To determine the etiological role of de novo mutations (DNMs) in IEDs.

Main Methods:

• Retrospective review of a large cohort of proband-parent trios of Chinese origin.
• Clinical diagnosis by an ophthalmologist following detailed examination.
• Panel-based targeted exome sequencing of 792 IED-causative genes and flanking exons.

Main Results:

• Overall diagnostic yield of 48.67% (605/1243) across 22 subgroups.
• Identified 108 IED-causative genes, with the top 24 explaining 67% of solved cases.
• Disease-causing DNMs accounted for 6.76% of trios, with high rates in aniridia, Marfan syndrome/ectopia lentis, and retinoblastoma.

Conclusions:

• Trio-based genetic analysis demonstrates high accuracy and validity for diagnosing IEDs.
• The study quantifies the genetic burden of IEDs per gene, aiding etiological elucidation.
• Findings are crucial for genetic counseling and optimizing patient management strategies.