Whole-exome sequencing identification of novel DNAH5 mutations in a young patient with primary ciliary dyskinesia

Kano,Gen; Tsujii,Hisashi; Takeuchi,Kazuhiko; Nakatani,Kaname; Ikejiri,Makoto; Ogawa,Satoru; Kubo,Hisami; Nagao,Mizuho; Fujisawa,Takao

doi:10.3892/mmr.2016.5871

Whole-exome sequencing identification of novel DNAH5 mutations in a young patient with primary ciliary dyskinesia

Authors:
- Gen Kano
- Hisashi Tsujii
- Kazuhiko Takeuchi
- Kaname Nakatani
- Makoto Ikejiri
- Satoru Ogawa
- Hisami Kubo
- Mizuho Nagao
- Takao Fujisawa
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Affiliations: Department of Pediatrics, Kyoto‑Yamashiro General Medical Center, Kizugawashi, Kyoto 619‑0214, Japan, Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Division of Personalized Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Central Clinical Laboratories, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Electron Microscopy Research Center, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, School of Medicine, Mie University, Tsu, Mie 514‑8507, Japan, Department of Pediatrics, Mie National Hospital, Tsu, Mie 514‑0125, Japan
Published online on: October 21, 2016 https://doi.org/10.3892/mmr.2016.5871
Pages: 5077-5083
Copyright: © Kano 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 genetic disorder caused by structural and/or functional impairment of cilia throughout the whole body. Early diagnosis of PCD is important for the prevention of long‑term sequelae, however early diagnosis is a challenge due to the phenotypic heterogeneity of PCD. In the current study, the patient with PCD was diagnosed at nine years old following several efforts to control intractable airway symptoms. The patient experienced a chronic productive cough beginning in early childhood and had multiple episodes of pneumonia and otitis media with effusion and sinusitis. No situs inversus or other heterotaxias were reported. Serial chest X‑rays exhibited persistent atelectasis and bronchiectasis in the right middle lobe. When the patient was nine years old, electron microscopy of his cilia and genetic analysis were conducted. Electron microscopy of a biopsy specimen from the nasal mucosa indicated loss of the outer dynein arms. Whole‑exome analysis of the genome demonstrated the presence of compound heterozygous mutations in DNAH5: NM_001369.2:c.5983C>T, p.Arg1995X in exon 36 and NM_001369.2:c.9101delG, p.Gly3034ValfsX22 in exon 54; neither of which have been previously reported in the literature in a Japanese patient. Notably, this case is, to the best of our knowledge, the first reported case of PCD caused by the DNAH5 mutation in a Japanese patient.

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