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首页> 外文期刊>Ophthalmic genetics >A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1
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A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

机译：用亚瑟综合征1型患者CDH23中的一种新型剪接现场变体

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Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23. Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D. Materials and Methods: Case report. Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65. Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.
机译：背景：基因编辑在校正异常剪接方面已经显示出巨大的电位，并且CAS13已被鉴定为特别适用于靶向RNA。因此，它越来越重要，突出可能是可矫正的，特别是在太大而无法被AAV载体编码的基因中。大约20％的亚瑟型1例是CDH23中的突变引起的。目的：报告与Usher型1D相关的CDH23的新剪接位点突变。材料和方法：案例报告。结果：一名35岁的白种人女性，伴随着前庭功能障碍的前庭功能障碍，在两只眼中呈现6/12。眼底考试揭示了典型的视网膜色素粒子，具有耐温性光感受器层。下一代测序分析揭示了CDH23中的新型纯合变体C.9319 + 1G> T一致，其与映综合征1D型诊断一致。预计C.9319 + 1G> T变型将在外显子65 /内部65边界处影响拼接，这很可能导致外显子65的完全跳过。结论：我们描述了由A引起的典型enher综合征1d型1D的情况CDH23中的新型剪接位点变体。目前，CDH23相关视网膜变性没有治疗，部分是因为10KB的cDNA尺寸对于AAV载体基因增强疗法太大。替代策略包括CRISPR-CAS9腺嘌呤基础编辑器和RNA编辑，具有CRISPR-CAS13。单核苷酸编辑代表靶向CDH23中该变体的有希望的方法，以在该位置恢复野生型剪接供体部位。

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