State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Exp Eye Res. 2020 Oct;199:108165. doi: 10.1016/j.exer.2020.108165. Epub 2020 Jul 28.
Familial exudative vitreoretinopathy (FEVR) is an inherited disease characterized by abnormal development of retinal vasculature. KIF11 mutations were identified to be associated with FEVR in recent years. The purpose of this study was to investigate novel variants and describe associated ocular and extraocular phenotypes in FEVR patients with KIF11 mutations. Herein, 417 probands with clinical diagnosis of FEVR were enrolled. Genetic testing and ophthalmic examinations were performed in all subjects, and the genotype-phenotype correlation was analyzed. Overall, KIF11 mutation was identified in nine probands (9/417, 2.2%) among the patients with FEVR phenotype. There were six males and three females whose median age was six months (range: four months to six years old) at first visit. Among the detected mutations, five (55.6%) were frameshift, two (22.2%) were missense, one (11.1%) nonsense, and one (11.1%) splicing. Seven of these KIF11 mutations were detected as novel. Four (4/9, 44.4%) of the mutations were de novo. Clinical examinations showed that: four probands presented with bilateral falciform retinal fold; two with bilateral tractional retinal detachment; one was observed tractional retinal detachment in one eye and retinal fold in the other eye; one had falciform retinal fold in one eye and chorioretinal atrophy in the other eye; one exhibited rhegmatogenous retinal detachment in the left eye. Six of the probands were detected to have microcephaly. In conclusion: Most (5/9,55.6%) of the causative mutations were frameshift, and nearly half (4/9, 44.4%) of the mutations were de novo. Most (8/9, 88.9%) patients with KIF11 mutations showed typical ocular manifestations of severe FEVR. Majority (6/9, 66.7%) of the probands had a KIF11 mutation and were detected to have microcephaly. Seven of these harbored KIF11 mutations detected to be novel.
家族渗出性玻璃体视网膜病变（FEVR）是一种遗传性疾病，其特征为视网膜血管发育异常。近年来，已发现 KIF11 突变与 FEVR 相关。本研究旨在探讨 KIF11 突变的 FEVR 患者的新变异体，并描述相关的眼部和眼部以外的表型。本研究纳入了 417 例临床诊断为 FEVR 的患者。对所有患者进行基因检测和眼科检查，并分析基因型-表型相关性。总的来说，在 FEVR 表型患者中，发现了 9 名患者（9/417，2.2%）存在 KIF11 突变。其中 6 名男性和 3 名女性，首次就诊时的中位年龄为 6 个月（范围：4 个月至 6 岁）。在检测到的突变中，有 5 个（55.6%）为移码突变，2 个（22.2%）为错义突变，1 个（11.1%）为无义突变，1 个（11.1%）为剪接突变。其中 7 个为新发现的突变。有 4 个（4/9，44.4%）为新生突变。临床检查显示，4 名患者双侧出现镰状视网膜皱褶；2 名患者双侧出现牵拉性视网膜脱离；1 名患者左眼为牵拉性视网膜脱离，右眼为视网膜皱褶；1 名患者左眼为镰状视网膜皱褶，右眼为脉络膜视网膜萎缩；1 名患者左眼为孔源性视网膜脱离。其中 6 名患者被检测出存在小头畸形。综上所述，大多数（5/9，55.6%）致病突变是移码突变，近一半（4/9，44.4%）的突变是新生突变。大多数（8/9，88.9%）KIF11 突变患者表现出严重 FEVR 的典型眼部表现。大多数（6/9，66.7%）的患者携带 KIF11 突变，并被检测出存在小头畸形。其中 7 例携带的 KIF11 突变是新发现的。
