A study on the relationship between the Wnt receptor signaling pathway and severe retinopathy of prematurity

Abstract

Objective To study the relationship of Wnt receptor signaling pathway and severe retinopathy of prematurity (ROP). Method From January 2011 to June 2015, preterm infants with severe ROP admitted to the NICU of our hospital were enrolled prospectively . Preterm infants with similar gestational age, gender, and age (in days) admitted to our hospital during the same period were selected as the control group. FZD4, LRP5, and ND gene mutations in Wnt receptor signaling pathway were examined. Result A total of 61 Chinese preterm infants were screened for these three candidate genes of Wnt receptor signaling pathway, 32 in ROP group and 29 in control group. ND and FZD4 gene mutations were not found among all cases. Eight types of LRP5 mutations were found in 26 cases of ROP group, including 7 cases of Exon18 missense mutation [c.3989C>T; p. Ala1330Val (rs3736228)], 5 cases of Exon8 synonymous mutation (c.1647T>C; p. Phe549Phe), 5 cases of Exon6 intronic mutation[c.1412+ 8G>A (rs4988319)], 3 cases of Exon2 missense mutation [c.266A>G; p. Gln89Arg (rs41494349)], 2 cases of Exon21 intronic mutation [c.4349-17C>T (rs372086596)], 2 cases of Exon19 synonymous mutation (c.4089C>T; p. Asp1363Asp), one case of Exon9 synonymous mutation (c.1932G>A; p. Glu644Glu), and one case of Exon16 missense mutation (c.3580C>T; p. Arg1194Cys). Three types of LRP5 mutations were found in 6 cases of the control group, including 4 cases of Exon8 synonymous mutation, one case of Exon19 synonymous mutation, and one case of Exon9 synonymous mutation. The positive rates of Exon18 missense mutation and Exon6 intronic mutation in severe ROP group were significantly higher than the control group (P<0.05). Conclusion LRP5 gene mutations in Wnt receptor signaling pathway may be associated with the occurrence of severe ROP. Key words: Wnt signaling pathway; Retinopathy of prematurity; Gene