Inherited Retinal Disease

Tailored gene panel enhances diagnosis and refines treatments for IRDs

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A pioneering 319-gene panel targeting inherited retinal dystrophy (IRD) genes appears to be effective and have clinical utility, according to a multi-center retrospective cohort study.

The research successfully identified disease-causing variants in a substantial percentage of cases, leading to molecular diagnoses for 68.5% of the probands. Notably, the study provides comprehensive insights into the mutation spectrum of Taiwanese IRD patients, emphasizing the prevalence of certain genes and shedding light on previously unreported variants.

A total of 493 patients from 425 unrelated families participated in the study, all of whom were initially suspected of having IRD without prior genetic diagnoses. Rigorous ophthalmic and physical examinations, including the recording of extra-ocular features, were conducted alongside genetic testing utilizing the newly developed customized panel.

Retinitis pigmentosa (RP) emerged as the most prevalent initial clinical impression, accounting for 64.2% of cases. Additionally, 90.8% of the cohort exhibited the 5 most common IRD phenotypes: RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, and Bietti crystalline dystrophy.

Among the probands who received molecular diagnoses, the most commonly mutated genes included USH2A (13.7%), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%). Collectively, these genes accounted for 40.8% of the diagnoses, providing valuable insights into the genetic landscape of IRD in Taiwan.

The study also identified 87 unique unreported variants previously not associated with IRD, highlighting the potential for novel genetic discoveries. Furthermore, clinical diagnoses were refined for 7.22% of positive cases, underscoring the impact of this research on individual patient care.

Kao HJ, Lin TY, et al. Highly efficient capture approach for the identification of diverse inherited retinal disorders. NPJ Genom Med. 2024;9(1):4. doi: 10.1038/s41525-023-00388-3. PMID: 38195571; PMCID: PMC10776681.