Eda Didem Kurt-Şükür, Emel Timucin, Turgut Baştuğ, Fatih Ozaltin
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引用次数: 0
Abstract
Steroid-resistant nephrotic syndrome (SRNS) is a severe kidney disorder linked to over 60 genes, including NUP85, which plays a key role in nuclear pore function and glomerulogenesis. We identified a novel homozygous NUP85 variant (NM_024844.5: c.1379G > A, p.Arg460Gln) in a pediatric SRNS patient who also presented with cleft lip-palate and mild intellectual disability, marking the first reported association of these phenotypes with a NUP85 variant. Molecular dynamics simulations revealed that the variant destabilizes the protein's helix bundle, providing mechanistic insights into its potential pathogenic effects. This study broadens the known phenotypic spectrum of NUP85-related conditions and highlights the value of computational tools, such as molecular dynamics, in unraveling the impact of novel variants.
类固醇抵抗性肾病综合征（SRNS）是一种严重的肾脏疾病，与60多个基因相关，其中包括在核孔功能和肾小球发生中起关键作用的NUP85。我们在一名患有唇腭裂和轻度智力残疾的儿童SRNS患者中发现了一种新的纯合NUP85变异（NM_024844.5: c.1379G > a, p.Arg460Gln），这是首次报道这些表型与NUP85变异的关联。分子动力学模拟显示，这种变异破坏了蛋白质的螺旋束，为其潜在的致病作用提供了机制上的见解。这项研究拓宽了nup85相关疾病的已知表型谱，并强调了计算工具（如分子动力学）在揭示新变异影响方面的价值。
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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