Frontiers in Genetics (Dec 2022)
Homozygous mutation in DNAAF4 causes primary ciliary dyskinesia in a Chinese family
- Guoliang Jiang,
- Guoliang Jiang,
- Lijun Zou,
- Lijun Zou,
- Lingzhi Long,
- Lingzhi Long,
- Yijun He,
- Yijun He,
- Xin Lv,
- Xin Lv,
- Yuanyuan Han,
- Yuanyuan Han,
- Tingting Yao,
- Tingting Yao,
- Yan Zhang,
- Yan Zhang,
- Mao Jiang,
- Mao Jiang,
- Zhangzhe Peng,
- Zhangzhe Peng,
- Lijian Tao,
- Lijian Tao,
- Wei Xie,
- Wei Xie,
- Jie Meng,
- Jie Meng
Affiliations
- Guoliang Jiang
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Guoliang Jiang
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Lijun Zou
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Lijun Zou
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Lingzhi Long
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Lingzhi Long
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Yijun He
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Yijun He
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Xin Lv
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Xin Lv
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
- Yuanyuan Han
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Yuanyuan Han
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
- Tingting Yao
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Tingting Yao
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Yan Zhang
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Yan Zhang
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Mao Jiang
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Mao Jiang
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Zhangzhe Peng
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Zhangzhe Peng
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
- Lijian Tao
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Lijian Tao
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
- Wei Xie
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- Wei Xie
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China
- Jie Meng
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
- Jie Meng
- Hunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fgene.2022.1087818
- Journal volume & issue
-
Vol. 13
Abstract
Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder that affects the structure and function of motile cilia, leading to classic clinical phenotypes, such as situs inversus, chronic sinusitis, bronchiectasis, repeated pneumonia and infertility. In this study, we diagnosed a female patient with PCD who was born in a consanguineous family through classic clinical manifestations, transmission electron microscopy and immunofluorescence staining. A novel DNAAF4 variant NM_130810: c.1118G>A (p. G373E) was filtered through Whole-exome sequencing. Subsequently, we explored the effect of the mutation on DNAAF4 protein from three aspects: protein expression, stability and interaction with downstream DNAAF2 protein through a series of experiments, such as transfection of plasmids and Co-immunoprecipitation. Finally, we confirmed that the mutation of DNAAF4 lead to PCD by reducing the stability of DNAAF4 protein, but the expression and function of DNAAF4 protein were not affected.
Keywords
- primary ciliary dyskinesia
- female infertility
- DNAAF4 mutation
- pathogenic mechanism
- autosomal recessive inheritance
