Novel biallelicTRPM1variants in an elderly patient with complete congenital stationary night blindness
Novel biallelicTRPM1variants in an elderly patient with complete congenital stationary night blindness
复制标题
DOI：
10.1007/s10633-020-09798-5
复制
发表时间：
2020-10-17
影响因子：
1.4
通讯作者：
Nakano, Tadashi
中科院分区：
文献类型：
--
作者：
Hayashi, Takaaki;Mizobuchi, Kei;Nakano, Tadashi
背景：完全性先天性静止性夜盲(CSNB)患者是否在其一生中保持视功能，目前知之甚少。本报告的目的是描述一例老年女性完全性CSNB患者的临床和遗传学特征，我们随访了5年。方法采用全外显子组测序技术进行分子遗传学分析，检测致病突变。我们进行了全面的眼科检查，包括全场视网膜电图(ERG)。结果在患者中，Wes发现了TRPM1基因的两个新的变异体(c.1034delT；p.Phe345SerfsTer16和c.1880T>；A；p.Met627Lys)。她未受感染的女儿也有其中一种变种。这位患者报告说，她的视力自小学以来一直没有变化。在68岁时，眼底和眼底自发荧光成像除了有轻微的近视改变外，没有明显的发现。Goldmann视野检查显示所有V-4E、I-4E、I-3E和I-2E等值线均保留视野。光学相干断层扫描显示保留的视网膜厚度和板层。杆状ERG无反应；亮闪光ERG呈电负性构型，a波减少最少；锥形和30-Hz闪光ERG反应减少最少。总体而言，双极通路功能障碍的ERG结果与完全性CSNB是一致的。结论这是报道的年龄最大的患者，具有完整的CSNB和双等位基因TRPM1变异。我们的眼科研究结果表明，一些患有TRPM1相关CSNB的患者在以后的生活中可能表现出保留的视网膜功能。
Background Little is known about whether patients with complete congenital stationary night blindness (CSNB) maintain visual function throughout their lifetime. The purpose of this report was to describe clinical and genetic features of an elderly female patient with complete CSNB that we followed for 5 years. Methods Molecular genetic analysis using whole-exome sequencing (WES) was performed to detect disease-causing variants. We performed a comprehensive ophthalmic examination including full-field electroretinography (ERG). Results In the patient, WES identified two novel variants (c.1034delT; p.Phe345SerfsTer16 and c.1880T>A; p.Met627Lys) in theTRPM1gene. Her unaffected daughter has one of the variants. The patient reported that her visual acuity has remained unchanged since elementary school. At the age of 68 years old, fundus and fundus autofluorescence imaging showed no remarkable findings except for mild myopic changes. Goldmann perimetry showed preserved visual fields with all V-4e, I-4e, I-3e and I-2e isopters. Optical coherence tomography demonstrated preserved retinal thickness and lamination. Rod ERG showed no response; bright-flash ERG showed an electronegative configuration with minimally reduced a-waves, and cone and 30-Hz flicker ERG showed minimally reduced responses. Overall, the ERG findings of ON bipolar pathway dysfunction were consistent with complete CSNB. Conclusions This is the oldest reported patient with complete CSNB and biallelicTRPM1variants. Our ophthalmic findings suggest that some patients withTRPM1-related CSNB may exhibit preserved retinal function later in life.