PDF(Pubmed)
Abstract：
OBJECTIVE: Retinoschisis is a distinctive condition characterized by intraretinal layer clefts, primarily associated with X-linked recessive inheritance due to RS1 gene mutations. This study aims to uncover the RS1 mutation spectrum in a cohort of 22 X-linked retinoschisis cases from South India and emphasizes the genotypic and phenotypic associations within patients harboring only RS1 mutations.
METHODS: A total of 22 probands were suspected of having X-linked retinoschisis. All study subjects underwent ophthalmic investigations, including assessments of visual acuity, fundus examination, optical coherence tomography (OCT), and electroretinogram (ERG). RS1 gene screening was conducted using Sanger sequencing, and the pathogenicity of the variants was assessed through Sorting Intolerant from Tolerant (SIFT) and PolyPhen-2 in silico tools.
RESULTS: The study found that the probands had an average visual acuity of 0.79 ± 0.39 log of minimum angle of resolution (logMAR), ranging from 0.17 to 1.77. During fundus examination, the probands exhibited a characteristic spoke wheel-like pattern in the macular region. Furthermore, OCT analysis revealed distinct alterations in the inner retinal microstructure, and ERG results consistently showed a reduction in b-wave amplitude. Eventually, Sanger sequencing results showed hemizygous mutations in the RS1 gene in only 12 probands, including a novel missense mutation in the RS1 gene\'s signal sequence.
CONCLUSIONS: This study provides valuable insights into the spectrum of RS1 mutations in X-linked retinoschisis probands from South India. It reveals distinct genotypic-phenotypic associations and highlights the clinical manifestations associated with the disease pathogenesis.
METHODS: A total of 22 probands were suspected of having X-linked retinoschisis. All study subjects underwent ophthalmic investigations, including assessments of visual acuity, fundus examination, optical coherence tomography (OCT), and electroretinogram (ERG). RS1 gene screening was conducted using Sanger sequencing, and the pathogenicity of the variants was assessed through Sorting Intolerant from Tolerant (SIFT) and PolyPhen-2 in silico tools.
RESULTS: The study found that the probands had an average visual acuity of 0.79 ± 0.39 log of minimum angle of resolution (logMAR), ranging from 0.17 to 1.77. During fundus examination, the probands exhibited a characteristic spoke wheel-like pattern in the macular region. Furthermore, OCT analysis revealed distinct alterations in the inner retinal microstructure, and ERG results consistently showed a reduction in b-wave amplitude. Eventually, Sanger sequencing results showed hemizygous mutations in the RS1 gene in only 12 probands, including a novel missense mutation in the RS1 gene\'s signal sequence.
CONCLUSIONS: This study provides valuable insights into the spectrum of RS1 mutations in X-linked retinoschisis probands from South India. It reveals distinct genotypic-phenotypic associations and highlights the clinical manifestations associated with the disease pathogenesis.
摘要：
目的：视网膜裂孔是一种独特的疾病，其特征是视网膜层裂，主要与由于RS1基因突变导致的X连锁隐性遗传有关。这项研究旨在揭示来自印度南部的22例X连锁视网膜裂孔病例中的RS1突变谱，并强调仅具有RS1突变的患者体内的基因型和表型关联。
方法：共有22名先证者被怀疑患有X连锁视网膜裂。所有研究对象都接受了眼科调查，包括视力评估，眼底检查,光学相干断层扫描(OCT),和视网膜电图（ERG）。使用Sanger测序进行RS1基因筛选，并且通过从耐受中筛选不耐受(SIFT)和PolyPhen-2在硅胶工具中评估变体的致病性。
结果：研究发现，先证者的最小分辨率角（logMAR）的平均视力为0.79±0.39log，范围从0.17到1.77。眼底检查时,先证者在黄斑区表现出特征性的轮辐状图案。此外，OCT分析显示视网膜内部微结构有明显改变，ERG结果一致显示b波振幅降低。最终,Sanger测序结果显示仅12名先证者的RS1基因发生半合子突变,在RS1基因的信号序列中包含一个新的错义突变。
结论：这项研究为来自印度南部的X-连锁视网膜裂先证者的RS1突变谱提供了有价值的见解。它揭示了不同的基因型-表型关联，并突出了与疾病发病机理相关的临床表现。
方法：共有22名先证者被怀疑患有X连锁视网膜裂。所有研究对象都接受了眼科调查，包括视力评估，眼底检查,光学相干断层扫描(OCT),和视网膜电图（ERG）。使用Sanger测序进行RS1基因筛选，并且通过从耐受中筛选不耐受(SIFT)和PolyPhen-2在硅胶工具中评估变体的致病性。
结果：研究发现，先证者的最小分辨率角（logMAR）的平均视力为0.79±0.39log，范围从0.17到1.77。眼底检查时,先证者在黄斑区表现出特征性的轮辐状图案。此外，OCT分析显示视网膜内部微结构有明显改变，ERG结果一致显示b波振幅降低。最终,Sanger测序结果显示仅12名先证者的RS1基因发生半合子突变,在RS1基因的信号序列中包含一个新的错义突变。
结论：这项研究为来自印度南部的X-连锁视网膜裂先证者的RS1突变谱提供了有价值的见解。它揭示了不同的基因型-表型关联，并突出了与疾病发病机理相关的临床表现。
