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Abstract：
Background: Congenital Stationary Night Blindness (CSNB) is a clinically and genetically heterogenous inherited retinal disorder associated with nystagmus, myopia, strabismus, defective dark adaptation, and decreased vision. Pathogenic variants in at least 17 genes have been associated with CSNB, where a hemizygous variant of NYX causing an X-linked form of the disorder is among the commonest causes.Materials and Methods: A retrospective chart review of a single pedigree was performed. Three pediatric patients underwent ophthalmic examinations, visual electrophysiology, and ocular imaging. Molecular genetic testing for CSNB was pursued where clinically indicated.Results: Two male siblings demonstrated clinical and electroretinographic evidence of complete CSNB. Genetic testing identified a NYX pathogenic, in-frame deletion in both children. Targeted variant analysis of the mother failed to identify the variant in two independent samples, most consistent with mosaicism.Conclusions: Clinical and molecular analyses within the described family demonstrate the possibility of maternal mosaicism in NYX-related CSNB. The importance of cascade molecular testing is highlighted. The prospect of somatic or germline mosaicism in NYX-related CSNB informs genetic counseling, genetic testing decisions, and risk assessment in affected families.
摘要：
背景：先天性固定夜盲（CSNB）是一种临床和遗传异质性遗传性视网膜疾病，与眼球震颤有关，近视,斜视,有缺陷的暗适应，视力下降。至少有17个基因的致病变异与CSNB相关，导致X连锁形式的NYX的半合子变体是最常见的原因之一。材料和方法：对单个家系进行回顾性图表回顾。三名儿科患者接受了眼科检查，视觉电生理学，和眼睛成像。在临床上需要进行CSNB的分子遗传检测。结果：两名男性兄弟姐妹表现出完整CSNB的临床和视网膜电图证据。基因检测确定了NYX的致病性，在两个子项中的帧内删除。母亲的靶向变异分析未能在两个独立样本中识别变异，最符合马赛克。结论：所述家庭中的临床和分子分析表明，在NYX相关的CSNB中，母亲镶嵌的可能性。强调了级联分子测试的重要性。在NYX相关的CSNB中，体细胞或种系镶嵌的前景告知遗传咨询，基因检测决定,以及受影响家庭的风险评估。
