Novel dynein axonemal assembly factor 1 mutations identified using whole‑exome sequencing in patients with primary ciliary dyskinesia

Zhou,Lei; Li,Zhuozhe; Du,Chunling; Chen,Cuicui; Sun,Yingxin; Gu,Liang; Zhou,Feng; Song,Yuanlin

doi:10.3892/mmr.2020.11562

Novel dynein axonemal assembly factor 1 mutations identified using whole‑exome sequencing in patients with primary ciliary dyskinesia

Authors:
- Lei Zhou
- Zhuozhe Li
- Chunling Du
- Cuicui Chen
- Yingxin Sun
- Liang Gu
- Feng Zhou
- Yuanlin Song
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Affiliations: Department of Pulmonary Medicine, Qingpu Branch of Zhongshan Hospital, Shanghai 201700, P.R. China, 2Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: October 6, 2020 https://doi.org/10.3892/mmr.2020.11562
Pages: 4707-4715
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder caused by dysfunction of the cilia and flagella; however, causative genetic defects have not been detected in all patients with PCD. Seven Chinese Han patients with Kartagener syndrome were enrolled onto the present study. Transmission electron microscopy (TEM) was performed to evaluate the cilial defects and whole‑exome sequencing was used to analyze relevant genetic variations in all patients. In two of the seven patients with PCD, four novel dynein axonemal assembly factor 1 (DNAAF1) mutations were identified (NM_178452.6:c.3G>A, c.124+1G>C, c.509delG and c.943A>T) in three alleles. Both of these patients had long‑standing infertility. Their chest computed tomography results showed bronchiectasis, lung infections and situs inversus, and paranasal computed tomography revealed sinusitis. Semen analysis of the male patient showed poor sperm motility. TEM showed defects in the inner and outer dynein arms in both patients. The DNAAF1 sequences of family members were then analyzed. Bioinformatics analysis indicated that these mutations may be the cause of the cilial defects in these two probands. Thus, the present study identified novel PCD‑causing mutations in DNAAF1 in two patients with PCD. These genetic variations were predicted to alter DNAAF1 amino acid residues and lead to loss of function, thereby inhibiting cilia‑mediated motility. Accordingly, the two probands had PCD symptoms, and one of them died due to PCD‑associated complications.

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