Medical Genetics Division, Department of Pediatrics, King Abdullah specialized Children's Hospital, King Abdulaziz Medical City, P. O Box 22490, Riyadh, 11426, Saudi Arabia.
Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia.
BMC Pulm Med. 2020 May 15;20(1):141. doi: 10.1186/s12890-020-1175-1.
Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing.
Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells.
NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.
原发性纤毛运动障碍（PCD）也称为不动纤毛综合征，是一种常染色体隐性纤毛功能障碍疾病，导致儿童呼吸系统黏液潴留。随着遗传和分子检测技术的进步，我们对这种破坏性疾病的病理生理方面的认识不断增加。
在这里，我们报告了两例具有 PCD 典型临床和影像学表现的同胞。通过全外显子组测序，我们在 NEK10 基因中发现了一个纯合截断变异（c.3402T>A）；p.（Tyr1134*）。Western blot 分析显示患者细胞中 NEK10 蛋白表达减少。
NEK10 在纤毛组装的有丝后过程中发挥核心作用，在生理和病理状态下调节纤毛长度和功能。本研究强调了鉴定高度异质性疾病致病变异的挑战，并报告了 NEK10 中一个新变异的鉴定，该变异最近与 PCD 相关。
