Hiraoka Miki, Takahashi Hiroshi, Orimo Hideo, Hiraoka Miina, Ogata Tsutomu, Azuma Noriyuki
Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Mol Vis. 2010 Dec 5;16:2572-7.
To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the wingless/int1 (Wnt) receptor signaling pathway-FZD4 for frizzled 4, LRP5 for low-density lipoprotein receptor-related protein 5, and ND for Norrie disease protein-are associated with the development of FEVR.
In the present study, 17 Japanese patients with advanced ROP were screened for these three candidate genes of FEVR. Genomic DNA from each patient was subjected to PCR and direct sequencing of the ND, FZD4, and LRP5 genes.
One patient had a heterozygous mutation in the 5' untranslated region of the ND gene. Another had a leucine insertion in the signal peptide of LRP5. None showed any mutation in FZD4.
These findings suggest that genetic changes in the Wnt receptor signaling pathway associate to the development of advanced ROP.
评估基因因素在早产儿视网膜病变（ROP）中的作用。虽然ROP通常与低出生体重和低胎龄相关，但这些因素不一定能预测ROP的严重程度。人们已经考虑了包括基因变异在内的其他因素的可能作用。家族性渗出性玻璃体视网膜病变（FEVR）是一种遗传性玻璃体视网膜疾病，其临床表现与ROP相似。与FEVR发病相关的三个基因涉及无翅/整合1（Wnt）受体信号通路——卷曲蛋白4（FZD4）、低密度脂蛋白受体相关蛋白5（LRP5）和诺里病蛋白（ND）。
在本研究中，对17例晚期ROP日本患者进行了这三个FEVR候选基因的筛查。对每位患者的基因组DNA进行PCR扩增，并对ND、FZD4和LRP5基因进行直接测序。
1例患者的ND基因5'非翻译区存在杂合突变。另1例患者的LRP5信号肽中有亮氨酸插入。FZD4未发现任何突变。
这些发现表明，Wnt受体信号通路中的基因变化与晚期ROP的发生有关。
