目的和原理:内部视网膜由三个视网膜内毛细血管丛提供,而外部视网膜由脉络膜循环提供:NDP对于正常的视网膜内血管形成至关重要。NDP(Xp11.3)的致病变异可能导致与听力损失(诺里病)相关的严重视网膜表型或中度视网膜表型(家族性渗出性玻璃体视网膜病变,FEVR)。然而,关于NDP变异体的性质或位置是否可预测严重程度,目前尚不清楚.在此系统评价中,我们总结了所有报道的NDP变体,并得出结论,NDP变体的性质是否可以预测导致的眼部病理以及相关的听力损失和智力障碍的严重程度。发现:据报道,NDP基因中的201种不同变体是致病的。可能由引起疾病的NDP变异导致的病理表型相当多样,但通常包括一致的特征群(视网膜血管形成减少,渗出,持续的胎儿脉管系统,牵引性/渗出性视网膜脱离,智力残疾和听力损失)随严重程度而变化。以前的评论没有发现引起FEVR或Norrie疾病的NDP突变的性质的明确模式,除了影响半胱氨酸残基的突变与Norrie病相关外,如果NDP突变导致翻译提前终止而不是错义相关的氨基酸变化,则Norrie病患者的视力丧失往往更严重.以前的评论的主要局限性是作者对Norrie病和FEVR的病例定义存在差异。因此,我们仅根据视网膜疾病的严重程度将患者分为两组。在不止一名患者中描述的已报告的致病变异中,我们发现,任何给定的变异每次报告时都会导致同等严重程度的视网膜病变,只有极少数例外.因此,我们得出结论,特定的NDP突变通常在每次出现时都会导致一致的视网膜表型。不同作者对同一变异导致FEVR或Norrie疾病冲突的报告主要是由于作者各自病例定义的差异而不是疾病严重程度的真实差异。
Aims and Rationale: The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR). However, little is known about whether the nature or location of the NDP variant is predictive of severity. In this systematic
review we summarise all reported NDP variants and draw conclusions about whether the nature of the NDP variant is predictive of the severity of the resulting ocular pathology and associated hearing loss and intellectual disability. Findings: 201 different variants in the NDP gene have been reported as disease-causing. The pathological phenotype that may result from a disease-causing NDP variant is quite diverse but generally comprises a consistent cluster of features (retinal hypovascularisation, exudation, persistent foetal vasculature, tractional/exudative retinal detachment, intellectual disability and hearing loss) that vary predictably with severity. Previous reviews have found no clear pattern in the nature of NDP mutations that cause either FEVR or Norrie disease, with the exception that mutations affecting cysteine residues have been associated with Norrie Disease and that visual loss amongst patients with Norrie disease tends to be more severe if the NDP mutation results in an early termination of translation as opposed to a missense related amino acid change. A key limitation of previous reviews has been variability in the case definition of Norrie disease and FEVR amongst authors. We thus reclassified patients into two groups based only on the severity of their retinal disease. Of the reported pathogenic variants that have been described in more than one patient, we found that any given variant caused an equivalent severity of retinopathy each time it was reported with very few exceptions. We therefore conclude that specific NDP mutations generally result in a consistent retinal phenotype each time they arise. Reports by different authors of the same variant causing either FEVR or Norrie disease conflict primarily due to variability in the authors\' respective case definitions rather than true differences in disease severity.