Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of PRDM13 causing North Carolina macular dystrophy in Korea.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2024-02-19 eCollection Date: 2024-01-01

Yuri Seo, Kwangsic Joo, Junwon Lee, Amber Diaz, Sohyun Jang, Timothy J Cherry, Kinga M Bujakowska, Jinu Han, Se Joon Woo, Kent W Small

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引用次数: 0

Abstract

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families.

Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools.

Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13.

Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.

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PRDM13 的 DNase1 超敏位点中的两个新型非编码单核苷酸变异导致韩国的北卡罗来纳州黄斑营养不良症。

目的：北卡罗来纳州黄斑营养不良症（NCMD）的致病变异在东亚人群中鲜有报道。在此，我们报告了 2 个韩国家庭中的 NCMD 新型变异体：方法：通过基因组测序分析了与 NCMD 相关的区域，并根据小等位基因频率（0.5%）和杂合度筛选出变异体。使用多种计算工具对非编码变异进行了功能注释：我们在 A 家系和 B 家系中分别发现了 PRDM13 上游的两个罕见新型变异，即 chr6:g.99,598,914T>C (hg38; V17) 和 chr6:g.99,598,926G>A (hg38; V18)。在家族 1 中，观察到 2 级 NCMD，右眼和左眼的最佳矫正视力分别为 20/25 和 20/200。在家族 B 中，所有受影响的个体都患有 1 级 NCMD，眼窝处有特征性的融合性色素沉着，双眼最佳矫正视力均为 20/20。这两个变异位于已报道的 DNase1 超敏位点 V10 变异的下游 10-22 bp。该位点与进行性双焦点脉络膜视网膜萎缩和先天性后极性脉络膜视网膜肥厚有关，位于 PRDM13 的假定增强子位点：我们在韩国人群中发现了两个新的 NCMD 变异，并进一步验证了 PRDM13 上游 DNase1 超敏位点的调控作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.