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Jinu Han, Seung-Tae Lee, Jong Rak Choi, John Hoon Rim, Hye Won Park, Sueng-Han Han; Personalized diagnosis and management of inherited pediatric ophthalmic diseases by Next-Generation Sequencing . Invest. Ophthalmol. Vis. Sci. 2018;59(9):5400.
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Pediatric ophthalmologists encounter various inherited ophthalmic diseases with significant genetic heterogeneity. Accurate diagnosis requires a high degree of clinical expertise. The aim of this study is to assess clinical utility of next-generation sequencing (NGS) in pediatric ophthalmology clinic.
A single-center retrospective case series involving 142 unrelated, consecutive patients in pediatric ophthalmology and neuro-ophthalmology clinic who underwent genetic testing between June 2015 and November 2017. NGS analysis was performed using a target panel that included 113 genes associated with INS (n=48) or 429 genes associated with known ocular phenotypes (n=93) or a TruSight One sequencing panel that included 4813 genes associated with known human phenotypes (n=1). Patients underwent detailed ophthalmic examinations, including electroretinogram and optical coherence tomography, if feasible.
Among the 143 patients, 80 (56%) were men and all patients were of single ethnicity (Korean), except 1 patient. The mean age at genetic testing was 12.3 ± 10.6 years. Variants that were highly likely to be causative were identified in 95 of the 143 patients, corresponding to a molecular diagnostic yield of 66.4% (95% CI: 50.8~73.5%). The most frequent mutated genes were FRMD7 (n=10) and NMNAT1 (n=7) in our cohort. Early molecular diagnosis of Senior Loken syndrome enabled physician to prepare kidney transplantation earlier and prompt recognition of Stickler syndrome caused by COL2A1 mutations led to apply prophylactic trans-conjunctival cryotherapy to prevent retinal detachment.
These findings demonstrate the clinical utility of NGS in pediatric ophthalmology clinic, and NGS enabled us to make accurate molecular diagnosis and to alter clinical management. Accurate NGS application and robust genotype-phenotype correlations in early childhood not only facilitated early molecular diagnosis, but also led to improved management outcomes in these patients.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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