Identification of missense mutations in the Norrie disease gene associated with advanced retinopathy of prematurity

Background: Retinopathy of prematurity (ROP) is a retinal vascular disease occurring in infants with short gestational age and low birth weight and can lead to retinal detachment (ROP stages 4 and 5). X-linked familial exudative vitreoretinopathy is phenotypically similar to ROP and has been associated with mutations in the Norrie disease (ND) gene in some cases. Objective: To determine if similar mutations in the ND gene may play a role in the development of advanced ROP. Methods: Clinical examination and molecular genetic analysis were performed on 16 children, including 2 dizygotic and 1 monozygotic twin pairs, and their parents from 13 families. Results: Sequencing of the amplified products revealed missense mutations (R121W and L108P) in the third exon of the ND gene in 4 patients. These mutations were not present in an unaffected premature twin, 2 children with regressed stage 3 ROP, the parents, or in SO unrelated healthy control subjects. Conclusion: These findings suggest that mutations in the ND gene may play a role in the development of severe ROP in premature infants.