Department of Ophthalmology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Japan.
Transl Vis Sci Technol. 2021 Jun 1;10(7):18. doi: 10.1167/tvst.10.7.18.
To determine the clinical characteristics of patients and family members with familial exudative vitreoretinopathy (FEVR) caused by mutations in the KIF11 gene.
Twenty-one patients from 10 FEVR families with mutations in the KIF11 gene were studied. The retinal and systemic features were examined. The genetic analyses performed included Sanger sequencing of the KIF11 gene, whole exome sequencing, as well as array comparative genomic hybridization (CGH) analysis and multiple ligation probe assay (MLPA).
Sequence analysis revealed seven different KIF11 mutations. Array CGH with MLPA revealed two different exon deletions. All probands had advanced FEVR with retinal detachments (RDs) and microcephaly with or without developmental disabilities. Patients with bilateral RDs were more frequently associated with developmental disabilities (P = 0.023). Multimodal imaging of the family members revealed that six of nine patients without RDs (66%) had varying degrees of chorioretinopathy. The retinal folds in FEVR patients were associated with severe retinal avascularization. However, funduscopic changes in the peripheral retina were unremarkable in family members without RDs. A score representing the peripheral vascular anomalies determined from the fluorescein angiograms was lower than that of control eyes of patients with mutations of the Wnt signaling genes (P = 0.0029).
The probands with KIF11 mutations were associated with severe ocular and systemic pathologies, whereas affected family members showed highly variable clinical manifestations. Peripheral vascular anomalies can often be unremarkable in eyes without RDs.
These findings highlight more diverse mechanisms that underlie the pathological changes in patients with FEVR.
确定 KIF11 基因突变致家族性渗出性玻璃体视网膜病变（FEVR）患者及其家系成员的临床特征。
对 10 个 KIF11 基因突变致 FEVR 家系的 21 例患者进行研究。检查视网膜和全身特征。进行的遗传分析包括 KIF11 基因的 Sanger 测序、外显子组测序以及比较基因组杂交（CGH）分析和多重连接探针扩增（MLPA）。
序列分析发现 7 种不同的 KIF11 突变。CGH 与 MLPA 显示两种不同的外显子缺失。所有先证者均有进展性 FEVR 伴视网膜脱离（RD）和小头畸形伴或不伴发育障碍。双侧 RD 患者更常伴有发育障碍（P = 0.023）。对家系成员的多模态成像显示，9 例无 RD 的患者中有 6 例（66%）存在不同程度的脉络膜视网膜病变。FEVR 患者的视网膜皱褶与严重的视网膜无血管化有关。然而，无 RD 的家系成员周边视网膜的眼底改变无明显异常。从荧光素眼底血管造影确定的代表周边血管异常的评分低于 Wnt 信号基因突变患者的对照眼（P = 0.0029）。
KIF11 基因突变的先证者与严重的眼部和全身病变相关，而受影响的家系成员表现出高度可变的临床表现。无 RD 的眼中，周边血管异常通常不明显。
杨蔚然
