Norrie Disease Gene Mutations In An Ethnically Diverse Population With Retinopathy Of Prematurity

Abstract

Abstract: : Purpose: Varying rates of threshold retinopathy of prematurity (ROP) in different races may be genetically influenced. Norrie disease (NDP) gene mutations are associated with hereditary vascular diseases and have been identified in some patients with advanced ROP. We screened NDP in infants of different ethnicity, both with and without severe ROP, and ascertained parental carrier status. Methods: One hundred and fifty subjects of different ethnic backgrounds underwent screening of the entire 3–exon NDP gene. Seven unique primer pairs were developed and the 7 amplicons were optimized for denaturing high performance liquid chromatography and sequencing analyses. Three amplicons covered the coding region and promotor sequence, and 4 amplicons covered the 3'UTR. Demographic and ROP clinical data were collected. Results: There were 63 patients with severe ROP (> Stage 3), including 14 patients with pre–threshold disease and 37 patients with threshold disease in at least one eye. Additionally, 29 premature infants with no or mild ROP, 31 parents, and 27 wild–type controls were screened. There were 77 African–Americans (AA), 54 Caucasians, and 19 subjects of other races. Severe ROP occurred in 29 AA, 16 Caucasian, and 6 patients of other race (mean gestational age of 26.1 weeks; mean birth weight of 788.4 grams). Two sequence alterations were found, both in the 3'UTR of exon 3. A G to A polymorphism at mRNA position 824 was found in an AA female and male with prethreshold and threshold ROP, respectively. An A to G polymorphism at mRNA position 1103 was found in an affected AA male; his normal mother was heterozygous for this change. Conclusions: The rate of NDP polymorphisms in this large, ethnically diverse population is low. These results show that no association exists between NDP mutations and ROP in a large cohort of infants.

Keywords: retinopathy of prematurity • retinal development • gene screening