Congenital stationary night blindness (CSNB) is a heterogeneous group of non-progressive inherited retinal disorders with characteristic electroretinogram (ERG) abnormalities. Riggs and Schubert-Bornschein are subtypes of CSNB and demonstrate distinct ERG features. Riggs CSNB demonstrates selective rod photoreceptor dysfunction and occurs due to mutations in genes encoding proteins involved in rod phototransduction cascade; night blindness is the only symptom and eye examination is otherwise normal. Schubert-Bornschein CSNB is a consequence of impaired signal transmission between the photoreceptors and bipolar cells. Schubert-Bornschein CSNB is subdivided into complete CSNB with an ON bipolar signaling defect and incomplete CSNB with both ON and OFF pathway involvement. Both subtypes are associated with variable degrees of night blindness or photophobia, reduced visual acuity, high myopia, and nystagmus. Whole-exome sequencing of a family screened negative for mutations in genes associated with CSNB identified biallelic mutations in the guanine nucleotide-binding protein subunit beta-3 gene (GNB3). Two siblings were compound heterozygous for a deletion (c.170_172delAGA [p.Lys57del]) and a nonsense mutation (c.1017G>A [p.Trp339*]). The maternal aunt was homozygous for the nonsense mutation (c.1017G>A [p.Trp339*]). Mutational analysis of GNB3 in a cohort of 58 subjects with CSNB identified a sporadic case individual with a homozygous GNB3 mutation (c.200C>T [p.Ser67Phe]). GNB3 encodes the beta subunit of G protein heterotrimer (G alpha beta gamma) and is known to modulate ON bipolar cell signaling and cone transducin function in mice. Affected human subjects showed an unusual CSNB phenotype with variable degrees of ON bipolar dysfunction and reduced cone sensitivity. This unique retinal disorder with dual anomaly in visual processing expands our knowledge about retinal signaling.
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机译:先天性静止性夜盲症(CSNB)是一组非渐进性遗传性视网膜疾病,具有特征性的视网膜电图(ERG)异常。 Riggs和Schubert-Bornschein是CSNB的亚型,表现出独特的ERG特征。 Riggs CSNB表现出选择性的棒状光感受器功能障碍,是由于编码与棒状光转导级联反应有关的蛋白质的基因突变而发生的。夜盲是唯一的症状,而眼科检查是正常的。 Schubert-Bornschein CSNB是光感受器与双极细胞之间信号传输受损的结果。 Schubert-Bornschein CSNB分为具有双极信号传导缺陷的完整CSNB和具有ON和OFF通路参与的不完整CSNB。这两种亚型均与夜盲或畏光程度不同,视力下降,高度近视和眼球震颤有关。一个家庭的全外显子测序对与CSNB相关的基因中的突变进行了阴性筛选,从而确定了鸟嘌呤核苷酸结合蛋白亚基beta-3基因(GNB3)中的双等位基因突变。两个兄弟姐妹是复合杂合子,分别是缺失(c.170_172delAGA [p.Lys57del])和无义突变(c.1017G> A [p.Trp339 *])。产妇的姨妈是无义突变的纯合子(c.1017G> A [p.Trp339 *])。在58名CSNB受试者中对GNB3进行了突变分析,确定了一个散发病例的纯合子GNB3突变(c.200C> T [p.Ser67Phe])。 GNB3编码G蛋白异三聚体(G alpha betaγ)的beta亚基,并已知在小鼠中调节ON双极细胞信号传导和视锥细胞转导蛋白功能。受影响的人类受试者显示出异常的CSNB表型,ON双极性功能障碍程度不同,视锥细胞敏感性降低。这种具有视觉处理双重异常的独特视网膜疾病扩大了我们对视网膜信号的认识。
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