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Mol Genet Genomic Med. 2020 Jan 20:e1137. doi: 10.1002/mgg3.1137. [Epub ahead of print]

Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population.

Author information

1
Department of Otorhinolaryngology, Head & Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
2
Department of Respiratory Medicine, Kanazawa University, Kanazawa, Japan.
3
Department of Anatomy and Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
4
Electron Microscopy Research Center, Mie University Graduate School of Medicine, Tsu, Japan.
5
Department of Central Laboratories, Mie University Hospital, Tsu, Japan.
6
Department of Respiratory Medicine, Tokyo Women's Medical University, Tokyo, Japan.
7
Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
8
Institute for Clinical Research, National Hospital Organization Mie National Hospital, Tsu, Japan.
9
Department of Genomic Medicine, Mie University Hospital, Tsu, Japan.

Abstract

BACKGROUND:

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The involvement of copy number variation (CNV) in the development of PCD is largely unknown.

METHODS:

We examined 93 Japanese patients with clinically suspected PCD from 84 unrelated families. CNV was examined either by exome sequencing of a PCD gene panel or by whole-exome sequencing (WES). The identified alterations were validated by PCR and Sanger sequencing. Nasal ciliary ultrastructure was examined by electron microscopy.

RESULTS:

Analysis of CNV by the panel or WES revealed a biallelic deletion in the dynein regulatory complex subunit 1 (DRC1) gene in 21 patients, which accounted for 49% of the PCD patients in whom a disease-causing gene was found. Sanger sequencing of the PCR product revealed a 27,748-bp biallelic deletion including exons 1-4 of DRC1 with identical breakpoints in all 21 patients. The ciliary ultrastructure of the patients with this CNV showed axonemal disorganization and the loss or gain of central microtubules.

CONCLUSION:

The deletion of DRC1 is the major cause of PCD in Japan and this alteration can cause various ciliary ultrastructural abnormalities.

KEYWORDS:

DRC1 ; copy number variation; ultrastructure

PMID:
31960620
DOI:
10.1002/mgg3.1137
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