Liu Zhen, He Mei, Luo Xuan, Pan Hu, Hu Juanli, Wan Zhengqing, Peng Yin, Luo Yixiao, Wang Hua, Mao Xiao
Key Laboratory for Birth Defects Research and Prevention of the National Health Commission, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, PR China.
School of Life Sciences, Central South University, Changsha, Hunan, PR China.
J Neurodev Disord. 2025 Jul 12;17(1):39. doi: 10.1186/s11689-025-09632-6.
Selenium, an essential micronutrient integrated into selenoproteins as selenocysteine, is fundamental to human health. These selenoproteins are vital for several physiological functions, including maintaining redox balance, safeguarding DNA, and metabolizing thyroid hormones, and are produced via complex pathways involving Sec-tRNA, the SECIS element, and specific proteins such as eEFSec. This study investigates a 4-year-old girl with global developmental delay and cerebellar atrophy, revealing compound heterozygous variants in the EEFSEC gene (p.V488Dfs*113 and p.R443P) through extensive genetic analysis and whole exome sequencing. Both functional prediction tools and structural analysis underscored the detrimental impact of the p.R443P variant. Notably, the patient's plasma exhibited elevated levels of oxidized fatty acid metabolites compared to those in healthy controls, suggesting an impairment in antioxidant mechanisms. This case link a human disease directly to variants in the EEFSEC gene, emphasizing its vital role in cerebellar atrophy and the broader implications for genetic disorders related to defects in selenoprotein synthesis. The results highlight the significance of genetic screening for EEFSEC variants in similar cases, potentially broadening the spectrum of known genetic subtypes associated with selenoprotein translation abnormalities.
硒作为一种必需的微量营养素，以硒代半胱氨酸的形式整合到硒蛋白中，对人类健康至关重要。这些硒蛋白对多种生理功能至关重要，包括维持氧化还原平衡、保护DNA和代谢甲状腺激素，并且是通过涉及硒代半胱氨酸转运RNA（Sec-tRNA）、硒代半胱氨酸插入序列（SECIS）元件以及特定蛋白质（如真核延伸因子硒蛋白特异性亚基（eEFSec））的复杂途径产生的。本研究调查了一名患有全面发育迟缓及小脑萎缩的4岁女童，通过广泛的基因分析和全外显子组测序，在EEFSEC基因中发现了复合杂合变异（p.V488Dfs*113和p.R443P）。功能预测工具和结构分析均强调了p.R443P变异的有害影响。值得注意的是，与健康对照相比，该患者血浆中氧化脂肪酸代谢产物水平升高，提示抗氧化机制受损。该病例将一种人类疾病直接与EEFSEC基因变异联系起来，强调了其在小脑萎缩中的重要作用以及对与硒蛋白合成缺陷相关的遗传疾病的更广泛影响。结果突出了在类似病例中对EEFSEC变异进行基因筛查的重要性，可能拓宽与硒蛋白翻译异常相关的已知遗传亚型谱。
