PDF(Pubmed)
Abstract：
UNASSIGNED: To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/β-catenin genes.
UNASSIGNED: This was a multicenter, cross-sectional, observational, and genetic study.
UNASSIGNED: Two-hundred eighty-one probands with FEVR were studied.
UNASSIGNED: Whole-exome sequence and/or Sanger sequence was performed for the Norrin/β-catenin genes, the FZD4, LRP5, TSPAN12, and NDP genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/β-catenin genes.
UNASSIGNED: The phenotype associated with or without pathogenic variants of the Norrin/β-catenin genes.
UNASSIGNED: One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the FZD4, 42 with the LRP5, 10 with the TSPAN12, and 12 with the NDP gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, P < 0.0001), progression during infancy (75.0% vs. 53.8%, P = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, P = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, P = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, P < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, P = 0.0346). Nine probands with NDP variants had features different from probands with typical Norrin/β-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease.
UNASSIGNED: The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/β-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
UNASSIGNED: This was a multicenter, cross-sectional, observational, and genetic study.
UNASSIGNED: Two-hundred eighty-one probands with FEVR were studied.
UNASSIGNED: Whole-exome sequence and/or Sanger sequence was performed for the Norrin/β-catenin genes, the FZD4, LRP5, TSPAN12, and NDP genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/β-catenin genes.
UNASSIGNED: The phenotype associated with or without pathogenic variants of the Norrin/β-catenin genes.
UNASSIGNED: One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the FZD4, 42 with the LRP5, 10 with the TSPAN12, and 12 with the NDP gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, P < 0.0001), progression during infancy (75.0% vs. 53.8%, P = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, P = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, P = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, P < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, P = 0.0346). Nine probands with NDP variants had features different from probands with typical Norrin/β-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease.
UNASSIGNED: The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/β-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
摘要：
■确定与或不与Norrin/β-catenin基因的致病性变体相关的家族性渗出性玻璃体视网膜病变（FEVR）的临床特征。
■这是一个多中心，横截面,观察,和基因研究。
■研究了具有FEVR的二百八十一个先证者。
■对Norrin/β-catenin基因进行全外显子组序列和/或Sanger序列，从先证者收集的血液中的FZD4，LRP5，TSPAN12和NDP基因。评估了有或没有致病性变体的先证者的临床症状以及Norrin/β-catenin基因之间的差异。
■与或不与Norrin/β-catenin基因的致病性变体相关的表型。
■一百零八个先证者（38.4％）在基因中具有88种不同的致病性或可能的致病性变体：FZD4为24，LRP5为42，TSPAN12为10，12为NDP基因。与173个没有致病变异的先证者相比，108位变异阳性先证者具有家族性易感性特征(63.9%vs.37.6%,P<0.0001),婴儿期进展（75.0%vs.53.8%,P=0.0004),2眼之间的不对称严重程度(50.0%vs.37.6%,P=0.0472),和非综合征特征(10.2%vs.17.3%,P=0.1185)。两组中出现更严重眼部疾病的最常见阶段是第4阶段（40.7％vs.34.7%）。然而,在更严重的眼睛中，3至5的晚期阶段在有变异的先证者中发现的频率高于没有变异的先证者(83.3%vs.58.4%,P<0.0001)。在变异阳性先证者中发现从1期或2期进展为孔源性视网膜脱离的患者频率较低（8.3％vs.17.3%,P=0.0346)。具有NDP变体的9个先证者具有与具有典型Norrin/β-catenin基因变体的先证者不同的特征，包括零星的，对称,系统特征与诺里病一致。
■结果表明，具有Norrin/β-catenin基因变异的患者的FEVR临床特征与具有其他病因的患者不同。我们建议诊断为FEVR儿童的临床医生进行基因检测，以便父母可以了解儿童的视力预后和一般健康状况。
■专有或商业披露可在本文末尾的脚注和披露中找到。
■这是一个多中心，横截面,观察,和基因研究。
■研究了具有FEVR的二百八十一个先证者。
■对Norrin/β-catenin基因进行全外显子组序列和/或Sanger序列，从先证者收集的血液中的FZD4，LRP5，TSPAN12和NDP基因。评估了有或没有致病性变体的先证者的临床症状以及Norrin/β-catenin基因之间的差异。
■与或不与Norrin/β-catenin基因的致病性变体相关的表型。
■一百零八个先证者（38.4％）在基因中具有88种不同的致病性或可能的致病性变体：FZD4为24，LRP5为42，TSPAN12为10，12为NDP基因。与173个没有致病变异的先证者相比，108位变异阳性先证者具有家族性易感性特征(63.9%vs.37.6%,P<0.0001),婴儿期进展（75.0%vs.53.8%,P=0.0004),2眼之间的不对称严重程度(50.0%vs.37.6%,P=0.0472),和非综合征特征(10.2%vs.17.3%,P=0.1185)。两组中出现更严重眼部疾病的最常见阶段是第4阶段（40.7％vs.34.7%）。然而,在更严重的眼睛中，3至5的晚期阶段在有变异的先证者中发现的频率高于没有变异的先证者(83.3%vs.58.4%,P<0.0001)。在变异阳性先证者中发现从1期或2期进展为孔源性视网膜脱离的患者频率较低（8.3％vs.17.3%,P=0.0346)。具有NDP变体的9个先证者具有与具有典型Norrin/β-catenin基因变体的先证者不同的特征，包括零星的，对称,系统特征与诺里病一致。
■结果表明，具有Norrin/β-catenin基因变异的患者的FEVR临床特征与具有其他病因的患者不同。我们建议诊断为FEVR儿童的临床医生进行基因检测，以便父母可以了解儿童的视力预后和一般健康状况。
■专有或商业披露可在本文末尾的脚注和披露中找到。
