A Novel Homozygous Nonsense Pathogenic Variant of the CPAMD8 Gene Associated With Congenital Microcoria.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Jing-Fan Gao, Xin Jin, Jing-Rao Wang, Shu Wang, Hong Zhang
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引用次数: 0

Abstract

Congenital microcoria (MCOR) is a rare inherited ocular disorder. Here, we describe a novel nonsense variant in the CPAMD8 gene in a patient with MCOR. We conducted a comprehensive clinical examination of a patient diagnosed with MCOR and performed whole-exome sequencing to identify potential pathogenic variants. Additionally, bioinformatics prediction tools were employed to assess the impact of the identified variant on protein structure and function. The patient presented with hallmark features of MCOR, such as bilaterally constricted pupils and a poor response to mydriatic agents. A novel homozygous nonsense variant, c.2679C>G (p.Tyr893*), was identified in the CPAMD8 gene. Protein modeling revealed that the variant results in complete truncation of the C-terminal domain of CPAMD8, disrupting its functional domains and potentially affecting its biological activity. Furthermore, electrostatic potential energy analysis demonstrated increased surface asymmetry of the protein, suggesting that the variant may interfere with protein-molecule interactions. Previous studies have suggested a strong association between MCOR and deletions in the 13q32.1 region of chromosome 13; however, the specific pathogenic genes involved have remained unclear. In this study, we show that the nonsense variant c.2679C>G (p.Tyr893*) in CPAMD8 is associated with MCOR, providing new insights into the genetic basis of the disease.

与先天性小冠相关的camd8基因的一种新的纯合无义致病变异。
先天性小眼珠(MCOR)是一种罕见的遗传性眼部疾病。在这里,我们描述了MCOR患者中camd8基因的一种新的无义变异。我们对一名诊断为MCOR的患者进行了全面的临床检查,并进行了全外显子组测序以确定潜在的致病变异。此外,利用生物信息学预测工具评估鉴定的变异对蛋白质结构和功能的影响。患者表现出MCOR的标志性特征,如双侧瞳孔缩小和对放血剂反应差。在CPAMD8基因中发现了一个新的纯合无义变异c.2679C>G (p.t r893*)。蛋白质模型显示,该变异导致camd8的c端结构域完全截断,破坏其功能结构域,并可能影响其生物活性。此外,静电势能分析表明,该蛋白的表面不对称性增加,表明该变异可能干扰蛋白质-分子相互作用。先前的研究表明,MCOR与13号染色体13q32.1区域的缺失密切相关;然而,具体的致病基因仍不清楚。在这项研究中,我们发现camd8中的无义变异c.2679C >g (p.t r893*)与MCOR相关,为该病的遗传基础提供了新的见解。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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