在巴基斯坦神经元蜡样脂褐质沉积症患者中发现了新型潜在致病 CLN5 变异体。
Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis.
机构信息
Department of Biological Sciences, International Islamic University Islamabad, H-10, Islamabad 44000, Pakistan; Department of Neuromuscular disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Department of Neuromuscular disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
出版信息
J Neurol Sci. 2020 Jul 15;414:116826. doi: 10.1016/j.jns.2020.116826. Epub 2020 Apr 7.
BACKGROUND
Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progressive cognitive deterioration. This study aimed to identify causative gene variants in Pakistani consanguineous families diagnosed with NCL.
METHODS
After a thorough clinical and neuroradiological characterization, whole exome sequencing (WES) was performed in 3 patients from 2 unrelated families. Segregation analysis was subsequently performed through Sanger sequencing ANALYSIS: WES led to the identification of the 2 novel homozygous variants c.925_926del, (p.Leu309AlafsTer4) and c.477 T > C, (p.Cys159Arg).
CONCLUSION
In this study, we report two novel CLN5 cases in the Punjab region of Pakistan. Our observations will help clinicians observe and compare common and unique clinical features of NCL patients, further improving our current understanding of NCL.
背景
神经元蜡样脂褐质沉积症（NCL）是一种遗传性溶酶体贮积病，伴有进行性脑神经退行性变。蜡样脂褐质沉积症神经元蛋白 5（CLN5）的突变导致 CLN5 病，这是一种严重的疾病，其特征是癫痫发作、视力丧失、运动能力下降和进行性认知恶化。本研究旨在鉴定在巴基斯坦近亲家庭中诊断出的 NCL 的致病基因突变。
方法
对来自 2 个无关家庭的 3 名患者进行了全外显子组测序（WES），在进行了彻底的临床和神经放射学特征描述后。随后通过 Sanger 测序进行了分离分析。
结果
WES 导致鉴定出 2 个新的纯合子变体 c.925_926del，（p.Leu309AlafsTer4）和 c.477T>C，（p.Cys159Arg）。
结论
在这项研究中，我们报告了巴基斯坦旁遮普地区的两个新的 CLN5 病例。我们的观察结果将帮助临床医生观察和比较 NCL 患者的常见和独特临床特征，进一步提高我们对 NCL 的现有认识。
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