Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan.
Ophthalmic Genet. 2021 Aug;42(4):412-419. doi: 10.1080/13816810.2021.1904422. Epub 2021 Mar 26.
Complete congenital stationary night blindness (CSNB) is a retinal disorder thought to be non-progressive. The purpose of this study was to characterize the clinical and genetic findings of middle-aged and older adult patients with X-linked complete CSNB.
Three male CSNB patients (aged 62, 72, and 51 years) and one unaffected female carrier in a Japanese family were included in this study. Whole-exome sequencing (WES) was performed to determine the disease-causing variants. Co-segregation was confirmed in the family members. We performed a comprehensive ophthalmic examination on each patient.
In the 62-year-old patient, a novel hemizygous variant (c.648 C > A; p.Asn216Lys) of the gene was identified by WES analysis. The other two patients carried the variant hemizygously, and the unaffected carrier harbored the variant heterozygously. The clinical and electroretinography (ERG) findings were very similar among all three patients. Fundus images exhibited high myopic chorioretinal atrophy with long axial length. Ultra-wide field fundus autofluorescence images showed no retinal degenerative changes except for changes resulting from high myopia and previous retinal diseases. The ERG findings showed no response in rod ERG, electronegative configuration with preserved a-waves in standard/bright-flash ERG, and preserved responses in cone and 30-Hz flicker ERG, which were compared with age-matched controls with high myopia.
We identified a novel missense variant in a Japanese family with complete CSNB. Our clinical findings indicated that photoreceptor mediated ERG responses are well preserved even in middle-aged and older adult patients.
完全性先天性静止性夜盲症（CSNB）是一种被认为不可进展的视网膜疾病。本研究的目的是描述中年和老年 X 连锁完全性 CSNB 患者的临床和遗传发现。
本研究纳入了一个日本家系中的 3 名男性 CSNB 患者（62 岁、72 岁和 51 岁）和 1 名未受影响的女性携带者。进行全外显子组测序（WES）以确定致病变异。在家族成员中证实了共分离。对每位患者进行了全面的眼科检查。
在 62 岁的患者中，通过 WES 分析发现了一个新的半合子变异（c.648C>A；p.Asn216Lys）。另外两名患者携带该变异的半合子，未受影响的携带者则携带该变异的杂合子。所有三名患者的临床和视网膜电图（ERG）表现非常相似。眼底图像显示高度近视性脉络膜视网膜萎缩伴长眼轴。超广角眼底自发荧光图像除了高度近视和先前的视网膜疾病引起的改变外，没有显示出任何视网膜变性改变。ERG 结果显示，在 rod ERG 中没有反应，标准/明亮闪烁 ERG 中出现电阴性构型且保留 a 波，在 cone 和 30-Hz 闪烁 ERG 中保留反应，与高度近视的年龄匹配对照相比。
我们在一个日本家系中发现了一个新的错义 变异，该家系患有完全性 CSNB。我们的临床发现表明，即使在中年和老年患者中，光感受器介导的 ERG 反应也得到很好的保留。
