Wang Rongchun, Yang Danhui, Guo Ting, Lei Cheng, Chen Xu, Kang Xi, Qing Jie, Luo Hong
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Research Unit of Respiratory Disease, Central South University, Changsha, China.
Front Genet. 2021 Feb 26;12:652381. doi: 10.3389/fgene.2021.652381. eCollection 2021.
encodes a protein of 595 amino acids and contain three highly conserved coiled-coil domains, which is essential for cilia axoneme dynein arm assembly and docking. Primary ciliary dyskinesia (PCD) of deficiency are rarely reported. Female infertility in PCD related to variants has not been reported. Whole-exome and Sanger sequencing were used to identify the disease-related gene of the patient with PCD in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ODAD3 protein. The 35 year-old female patient exhibited chronic sinusitis, diffuse bronchiectasis, dextrocardia and infertility. We identified a novel homozygous variant in , c.1166_1169dupAGAC, p.(Leu391Aspfs105) in the PCD patient by exome sequencing and Sanger sequencing. This frameshift variant was predicted to be disease causing by bioinformatics analysis and was also not presented in the current authorized large genetic databases. Our study enriches the genetic spectrum and clinical phenotypes of variants in PCD and provide more evidence for future genetic counseling and gene-targeted therapy for this disease.
编码一个由595个氨基酸组成的蛋白质，并包含三个高度保守的卷曲螺旋结构域，这对纤毛轴丝动力蛋白臂的组装和对接至关重要。关于该蛋白缺乏导致的原发性纤毛运动障碍（PCD）的报道很少。尚未有关于与该蛋白变体相关的PCD患者女性不孕的报道。我们使用全外显子组测序和桑格测序来鉴定一个近亲中国家庭中PCD患者的疾病相关基因。应用结构域分析来预测该变体对ODAD3蛋白的影响。这位35岁的女性患者表现出慢性鼻窦炎、弥漫性支气管扩张、右位心和不孕。通过外显子组测序和桑格测序，我们在该PCD患者中鉴定出一个新的纯合变体，位于该基因上，c.1166_1169dupAGAC，p.(Leu391Aspfs105)。通过生物信息学分析预测这个移码变体是致病的，并且在当前已授权的大型遗传数据库中也未出现。我们的研究丰富了PCD中该蛋白变体的遗传谱和临床表型，并为该疾病未来的遗传咨询和基因靶向治疗提供了更多证据。
