State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China.
Genes (Basel). 2022 Apr 18;13(4):713. doi: 10.3390/genes13040713.
Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25/696). Among 25 KIF11 mutations, 80% (20/25) carried variants of loss of function and 48% (12/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1/70) of eyes with FEVR with mutations in other genes (p < 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12/70) of eyes with KIF11-associated retinopathy, and in 50% (39/78) of eyes with FEVR with mutations in other genes (p < 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.
本研究旨在报告大型家族渗出性玻璃体视网膜病变（FEVR）人群中 KIF11 突变的频率，扩展 KIF11 相关视网膜病变的临床谱，并将 KIF11 相关视网膜病变与其他基因突变引起的 FEVR 进行比较。
对 696 个 FEVR 家系的遗传数据进行了回顾性分析。分析了 KIF11 突变患者的眼部表型，并与其他基因突变（FZD4、TSPAN12、LRP5、NDP 和 JAG1）引起的 FEVR 患者进行了比较。
在 696 个 FEVR 家系的队列中，发现 3.6%（25/696）的家系存在致病 KIF11 突变。在 25 个 KIF11 突变中，80%（20/25）携带功能丧失变异，48%（12/25）为新生变异。表型多样。与其他基因突变引起的 FEVR 相比，KIF11 相关视网膜病变患者中观察到脉络膜视网膜发育不良 44.2%（31/70），而其他基因突变引起的 FEVR 患者中仅为 1.3%（1/70）（p<0.01）。KIF11 相关视网膜病变患者中观察到 17.1%（12/70）的周边血管增粗和变直（ISPV），而其他基因突变引起的 FEVR 患者中为 50%（39/78）（p<0.01）。
在我们的数据库中，FEVR 中 KIF11 突变的频率为 3.6%。KIF11 相关视网膜病变的表现多样，与其他基因引起的 FEVR 表型不同。脉络膜视网膜发育不良而非视网膜皱褶是 KIF11 相关视网膜病变的主要表现。ISPV 在 KIF11 相关视网膜病变中罕见。此外，我们的研究表明，大多数致病性 KIF11 突变是新生的。
