Identification of novel KIF11 mutations in patients with familial exudative vitreoretinopathy and a phenotypic analysis.
Identification of novel KIF11 mutations in patients with familial exudative vitreoretinopathy and a phenotypic analysis.
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家族性渗出性玻璃体视网膜病变患者中新型 KIF11 突变的鉴定和表型分析。
DOI：
10.1038/srep26564
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发表时间：
2016-05-23
影响因子：
4.6
通讯作者：
Zhao P
中科院分区：
文献类型：
--
作者：
Li JK;Fei P;Li Y;Huang QJ;Zhang Q;Zhang X;Rao YQ;Li J;Zhao P
KIF11 基因突变会导致一种罕见的常染色体显性遗传病，称为小头畸形，伴或不伴脉络膜视网膜病变、淋巴水肿或智力低下 (MCLMR)。最近，还发现此类突变与家族性渗出性玻璃体视网膜病变（FEVR）有关。在这里，我们报告了通过靶向基因捕获在 2015 年 3 月至 2015 年 11 月期间在我们诊所诊断的 142 名 FEVR 先证者队列中发现的 7 个新的 KIF11 突变。这些突变是：p.L171V、c.790-2A>C、p.Q525*、p.Q842*、p.S936*、p.L983fs 和p.R1025G。表型分析显示，所有受影响的先证者均具有晚期 FEVR（4 级或以上）。其中 3 例患有小头畸形，1 例患有脉络膜视网膜病变，这表明与 MCLMR 存在表型重叠。在受影响的先证者的家族中也发现了两种突变。一位携带 p.R1025G 突变的父母有无血管的周边视网膜和异常的循环血管。然而，一位携带 p.L983fs 的父母的视网膜正常，这表明该基因型的渗透不完全。我们的结果进一步证实 KIF11 以常染色体显性方式导致 FEVR。我们还建议在未来的实践中对 FEVR 患者进行 MCLMR 样特征检查，例如小头畸形、脉络膜视网膜病变，并对 MCLMR 患者进行宽视野眼底摄影。
KIF11 gene mutations cause a rare autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR). Recently, such mutations were also found to be associated with familial exudative vitreoretinopathy (FEVR). Here, we report 7 novel KIF11 mutations identified by targeted gene capture in a cohort of 142 probands with FEVR who were diagnosed in our clinic between March 2015 and November 2015. These mutations were: p.L171V, c.790-2A>C, p.Q525*, p.Q842*, p.S936*, p.L983fs and p.R1025G. Phenotypic analysis revealed that all of the affected probands had advanced FEVR (stage 4 or above). Three had microcephaly, and one had chorioretinopathy, which indicated a phenotypic overlap with MCLMR. Two mutations were also found in the families of the affected probands. One parent with a p.R1025G mutation had an avascular peripheral retina and abnormal looping vessels. However, one parent with p.L983fs had normal retina, which indicated incomplete penetration of the genotype. Our results further confirmed that KIF11 is causative of FEVR in an autosomal dominant manner. We also suggest the examination of MCLMR-like features, such as microcephaly, chorioretinopathy, for patients with FEVR and wide-field fundus photography for patients with MCLMR in future practice.