Yang Binyi, Lei Cheng, Yang Danhui, Lu Chenyang, Xu Yingjie, Wang Lin, Guo Ting, Wang Rongchun, Luo Hong
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.
Research Unit of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.
Pharmgenomics Pers Med. 2022 Jul 11;15:697-704. doi: 10.2147/PGPM.S365740. eCollection 2022.
encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by deficiency.
We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed.
We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in . The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal.
Our study identified a novel frameshift variant in causing PCD, enriched the genetic spectrum of variants, and verified that mutation can lead to only a PCD characteristic phenotype, while other -associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.
编码一种含有1012个氨基酸的蛋白质，它是基体和中心粒的组成部分，对纤毛的生物发生至关重要。在早期研究中报道其与X染色体连锁的畸形综合征有关，近期研究报道了几例由该基因缺陷导致的原发性纤毛运动障碍（PCD）病例。
我们报告一名31岁男性，患有复发性呼吸道感染，具有原发性纤毛运动障碍的典型表现。除呼吸道表现外，该患者还患有内脏反位、肥胖、胃食管反流和听力障碍。还观察到杵状指和轻度蜘蛛指。
我们进行了全外显子组测序，在该基因中鉴定出一个新的变异c.2795delA:p.(Lys932Argfs*3)。通过生物信息分析软件和美国医学遗传学与基因组学学会（ACMG）指南预测该半合子变异可能具有致病性。进行了高速视频显微镜（HSVM）、透射电子显微镜（TEM）和免疫荧光检查以分析呼吸道纤毛。在HSVM下观察到高摆动频率和僵硬的摆动模式，而TEM和免疫荧光检查未发现明显异常。精子鞭毛检查总体也正常。
我们的研究在该基因中鉴定出一个导致PCD的新的移码变异，丰富了该基因突变谱，并证实该基因突变仅导致PCD特征性表型，而不存在其他与该基因相关的综合征性症状，如畸形特征和肾脏症状。
