The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated to syndromic congenital retinal dystrophy
The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated to syndromic congenital retinal dystrophy
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DOI：
10.1136/bjophthalmol-2015-307555
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发表时间：
2016-06-01
影响因子：
4.1
通讯作者：
Khan, Arif O.
中科院分区：
文献类型：
--
作者：
Bifari, Inam N.;Elkhamary, Sahar M.;Khan, Arif O.
研究背景圆锥肾综合征是一种以骨骼和肾脏病变为特征的全身性骨骼纤毛病，由鞭毛内转运140衣原体同源基因（IFFT 140）的双等位基因突变引起。大多数研究都集中在综合征的特点，并由非眼科医生。方法回顾性连续病例系列（2010-2014）。结果确定了12例经证实的纯合突变受试者（11个血缘家庭; 7名男孩;在10个月至20岁，平均和中位年龄6.5岁和4岁）。除1例c.1541_1542delinsAA纯合子外，所有患者均为相同IFFT 140突变（c.1990G>A; p.Glu664Lys）纯合子。所有人自出生起视力差和眼球震颤，5岁后视力下降，手部动作或光感消失。在儿童早期，9人注意到盯着灯光，4人注意到有一个快乐的举止，高度远视是典型的，视网膜电图是不可记录的。1岁以前眼底外观大体正常，但此后出现营养不良。8名儿童患有发育迟缓，2名儿童手指短粗，1名儿童患有肾病，但4名儿童没有明显的眼外疾病，其中1名18岁，还有两名20多岁的受影响的哥哥姐姐，他们没有出现综合征，并且在学业上表现出色。结论隐性IFT 140突变会导致严重的先天性视网膜营养不良，伴有高度远视和经常早期喜光。发育迟缓是常见的，但不是普遍的，并不是所有的患者都有明显的眼外表现。c.1990 G>A突变代表阿拉伯半岛的奠基者效应或突变热点。
Background Conorenal syndrome is a systemic skeletal ciliopathy characterised by skeletal and renal findings and caused by biallelic mutations in the gene intraflagellar transport 140 Chlamydomonas homologue (IFT140). Most studies have focused on syndromic features and are by non-ophthalmologists. We highlight the ophthalmic phenotype.Methods Retrospective consecutive case series (2010-2014).Results Twelve subjects with confirmed homozygous mutations were identified (11 consanguineous families; 7 boys; assessed at age 10 months to 20 years, average and median age 6.5 and 4 years). All were homozygous for the same IFT140 mutation (c.1990G>A; p. Glu664Lys) except one who was homozygous for c.1541_1542delinsAA. All had poor vision and nystagmus since birth, with visual acuity after 5 years old of hand motions or light perception. In early childhood, nine were noted to stare at lights, four were noted to have a happy demeanour, high hyperopia was typical, and electroretinography was non-recordable. Fundus appearance was grossly normal before the age of 1 year but thereafter appeared dystrophic. Eight children had developmental delay, two had short stubby fingers, and one had renal disease, but four had no evident extraocular disease, including one aged 18 years who also had two older affected siblings in their twenties who remained non-syndromic and were excelling academically.Conclusions Recessive IFT140 mutations cause a severe congenital retinal dystrophy with high hyperopia and often early photophilia. Developmental delay is common but not universal and not all patients have obvious extraocular findings. The c.1990G>A mutation represents a founder effect or mutational hotspot on the Arabian Peninsula.