Bartiméus Institute for the Visually Impaired, Zeist, The Netherlands; MOVE Research Institute, Faculty of Human Movement Sciences, VU University, Amsterdam, The Netherlands.
Ophthalmology. 2013 Oct;120(10):2072-81. doi: 10.1016/j.ophtha.2013.03.002. Epub 2013 May 25.
To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2.
Clinic-based, longitudinal, multicenter study.
A total of 39 patients with CSNB1 from 29 families and 62 patients with CSNB2 from 43 families.
Patients underwent full ophthalmologic and electrophysiologic examinations. On the basis of standard electroretinograms (ERGs), patients were diagnosed with CSNB1 or CSNB2. Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in NYX, TRPM1, GRM6, and GPR179 in patients with CSNB1 and CACNA1F and CABP4 in patients with CSNB2.
Data included genetic cause of CSNB, refractive error, visual acuity, nystagmus, strabismus, night blindness, photophobia, color vision, dark adaptation (DA) curve, and standard ERGs.
A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a "square-wave" appearance in CSNB1 and a decreased b-wave in CSNB2. Mutations causing CSNB1 were found in NYX (20 patients, 13 families), TRPM1 (10 patients, 9 families), GRM6 (4 patients, 3 families), and GPR179 (2 patients, 1 family). Congenital stationary night blindness 2 was primarily caused by mutations in CACNA1F (55 patients, 37 families). Only 3 patients had causative mutations in CABP4 (2 families). Patients with CSNB1 mainly had rod-related problems, and patients with CSNB2 had rod- and cone-related problems. The visual acuity on average was better in CSNB1 (0.30 logarithm of the minimum angle of resolution [logMAR]) than in CSNB2 (0.52 logMAR). All patients with CSNB1 and only 54% of the patients with CSNB2 reported night blindness. The dark-adapted threshold was on average more elevated in CSNB1 (3.0 log) than in CSNB2 (1.8 log). The 3 patients with CABP4 had a relative low visual acuity, were hyperopic, had severe nonspecific color vision defects, and had only 1.0 log elevated DA threshold.
Congenital stationary night blindness 1, despite different causative mutations, shows 1 unique CSNB1 phenotype. Congenital stationary night blindness 2 caused by mutations in CABP4 merely shows cone-related problems and therefore appears to be distinct from CSNB2 caused by mutations in CACNA1F.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
研究 Schubert-Bornschein 型先天性静止性夜盲症（CSNB）的遗传病因相对频率，并确定 CSNB1 和 CSNB2 的基因型-表型相关性。
基于临床的、纵向的、多中心研究。
共有 29 个家系的 39 名 CSNB1 患者和 43 个家系的 62 名 CSNB2 患者。
患者接受全面的眼科和电生理检查。根据标准视网膜电图（ERG），将患者诊断为 CSNB1 或 CSNB2。通过对 CSNB1 患者的 NYX、TRPM1、GRM6 和 GPR179 以及 CSNB2 患者的 CACNA1F 和 CABP4 的整个编码区域进行直接 Sanger 测序，进行分子分析。
数据包括 CSNB 的遗传病因、屈光不正、视力、眼球震颤、斜视、夜盲、畏光、色觉、暗适应（DA）曲线和标准 ERG。
根据标准 ERG 做出 CSNB1 或 CSNB2 的诊断。光 ERG 是区分 CSNB1 和 CSNB2 最特异的标准，因为它在 CSNB1 中显示出“方波”外观，而在 CSNB2 中则显示出 b 波降低。导致 CSNB1 的突变发生在 NYX（20 名患者，13 个家系）、TRPM1（10 名患者，9 个家系）、GRM6（4 名患者，3 个家系）和 GPR179（2 名患者，1 个家系）。先天性静止性夜盲症 2 主要由 CACNA1F（55 名患者，37 个家系）的突变引起。只有 3 名患者存在 CABP4 的致病突变（2 个家系）。CSNB1 患者主要有杆状细胞相关问题，CSNB2 患者有杆状细胞和锥状细胞相关问题。CSNB1 的平均视力（0.30 最小角分辨率对数[logMAR]）优于 CSNB2（0.52 logMAR）。所有 CSNB1 患者（100%）和仅 54%的 CSNB2 患者报告有夜盲症。CSNB1 的暗适应阈值平均升高（3.0 log），而 CSNB2 为 1.8 log。3 名 CABP4 患者的视力相对较低，远视，有严重的非特异性色觉缺陷，且仅 1.0 log 的 DA 阈值升高。
尽管 CSNB1 的突变不同，但仍表现出 1 种独特的 CSNB1 表型。由 CABP4 突变引起的先天性静止性夜盲症 2 仅表现出锥状细胞相关问题，因此与由 CACNA1F 突变引起的 CSNB2 明显不同。
作者没有与本文讨论的任何材料有关的专有或商业利益。
