Mutational screening of AGRN, SLC39A5, SCO2, P4HA2, BSG, ZNF644, and CPSF1 in a Chinese cohort of 103 patients with nonsyndromic high myopia.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2021-12-07 eCollection Date: 2021-01-01

Yi-Han Zheng, Xue-Bi Cai, Lu-Qi Xia, Fang-Yue Zhou, Xin-Ran Wen, De-Fu Chen, Fang Han, Kai-Jing Zhou, Zi-Bing Jin, Wen-Juan Zhuang, Bing Lin

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引用次数: 0

Abstract

Purpose: High myopia (HM) is one of the leading causes of irreversible vision loss in the world. Many myopia loci have been uncovered with linkage analysis, genome-wide association studies, and sequencing analysis. Numerous pathogenic genes within these loci have been detected in a portion of HM cases. In the present study, we aimed to investigate the genetic basis of 103 patients with nonsyndromic HM, focusing on the reported causal genes.

Methods: A total of 103 affected individuals with nonsyndromic HM were recruited, including 101 patients with unrelated sporadic HM and a mother and son pair. All participants underwent comprehensive ophthalmic examinations, and genomic DNA samples were extracted from the peripheral blood. Whole exome sequencing was performed on the mother and son pair as well as on the unaffected father. Sanger sequencing was used to identify mutations in the remaining 101 patients. Bioinformatics analysis was subsequently applied to verify the mutations.

Results: An extremely rare mutation in AGRN (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in AGRN (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs*76 and c.1023_1024insA, p.P342Tfs*41 in SLC39A5; c.244_246delAAG, p.K82del in SCO2; c.545A>G, p.Y182C in P4HA2; c.415C>T, p.P139S in BSG; c.3266A>G, p.Y1089C in ZNF644; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in CPSF1. Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants.

Conclusions: We provide further evidence for the potential role of AGRN in HM inheritance and enlarged the current genetic spectrum of nonsyndromic HM by comprehensively screening the reported causal genes.

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中国103例非综合征性高度近视患者中agn、SLC39A5、SCO2、P4HA2、BSG、ZNF644和CPSF1的突变筛查

目的:高度近视(HM)是世界上导致不可逆视力丧失的主要原因之一。许多近视基因座已被连锁分析、全基因组关联研究和测序分析发现。在部分HM病例中发现了这些基因座内的许多致病基因。在本研究中，我们旨在研究103例非综合征性HM患者的遗传基础，重点关注已报道的致病基因。方法:共招募103例非综合征性HM患者，包括101例无关联的散发性HM患者和一对母子。所有参与者都接受了全面的眼科检查，并从外周血中提取了基因组DNA样本。对母亲和儿子以及未受影响的父亲进行了全外显子组测序。Sanger测序用于鉴定其余101例患者的突变。随后应用生物信息学分析来验证突变。结果:在母子对中发现了一个极其罕见的agn突变(c.2627A>T, p.K876M)，但在未受影响的父亲中未发现。另外两个突变发生在agn上(c. 4787c >T, p.P1596L/c)。5056G>A, p.G1686S)在两例无关患者中发现。在其余99例患者中的8例中，共检测到8个可能影响该蛋白功能的杂合变异体，包括SLC39A5中的c.1350delC, p.V451Cfs*76和c.1023_1024insA, p.P342Tfs*41;c.244_246delAAG, p.K82del in SCO2;c.545A>G, p.Y182C在P4HA2;c.415C>T, p.P139S;c.3266A>G, p.Y1089C in ZNF644;CPSF1中c.2252C>T, p.S751L和c.1708C>T, p.R570C。进行了多项生物信息学分析，并与地理位置匹配的对照组进行了比较，这支持了这些变异的潜在致病性。结论:通过对已报道的致病基因进行全面筛选，进一步证明了agn在HM遗传中的潜在作用，扩大了目前非综合征型HM的遗传谱。

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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.