Abstract
Purpose: Retinopathy of prematurity (ROP) is a major cause of childhood blindness worldwide; it is a proliferative retinal vascular disease in preterm infants. Some infants progress to severe disease despite absence of these clinical risk factors such as low birth weight, gestational age and oxygen. Genetic factors seem to have etiologic roles in retinopathy of prematurity (ROP). This matched case-control study examined genetic factors for ROP.Methods: Confirmed 71 severe ROP cases and gestational age, birth weight and days of oxygen therapy matched controls (1:1) were enrolled from September 2015 to August 2020. Exome sequencing was performed and accomplished by next-generation sequencing. Gene mutations on heritable retinal vascular diseases related to Norrin signaling pathway were analyzed. Results: Seven heterozygous variants in exon 2 and the 3′ UTR were identified in the FZD4 gene in 28 patients with ROP. Variants c.*3770A > T and c.*2971T > C were found to be significantly associated with ROP (P = 0.033 and P = 0.017 respectively). Screening of LPR5 revealed five heterozygous variants. The rate of variant c.575 + 6T > C was much higher in infants with ROP (P = 0.009). One variant in exon 3 (c.67-9delT) was found in the TSPAN12 gene in one infant with ROP, whereas another variant of TSPAN12, c.*1139A > T, was identified in both groups. Two variants of ZNF408, c.581_592del AGTGGTGACAGA and c.1007C > T, were found in infants with ROP, with the rate of change of the former being much higher in infants with ROP (P < 0.001 and P = 0.033 respectively). Conclusions: This study revealed genetic factors in Norrin signaling may contributed to the development and severity of ROP, which warrants further detailed investigation worldwide.
The Genetics and Clinical Variables of Retinopathy of Prematurity: A Matched Case Control Study
