Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1–4 of DRC1 in Japanese patients with recurrent sinopulmonary infection

• Published in: Molecular genetics & genomic medicine Vol. 8; no. 1; pp. e1033 - n/a
• Main Authors: Keicho, Naoto, Hijikata, Minako, Morimoto, Kozo, Homma, Sakae, Taguchi, Yoshio, Azuma, Arata, Kudoh, Shoji
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2020; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Alleles; Breakpoints; Bronchiolitis - diagnosis; Cilia - ultrastructure; Ciliary Motility Disorders - diagnosis; Ciliary Motility Disorders - genetics; Ciliary Motility Disorders - microbiology; Cystic fibrosis; Deoxyribonucleic acid; Diagnosis, Differential; diffuse panbronchiolitis; Disease; DNA; Dyspnea; Exons; Female; founder mutation; Gene Deletion; Gene frequency; Gene sequencing; Genes; Genetic screening; Genetic testing; Genetic Testing - methods; Genomics; Haemophilus Infections - diagnosis; Homozygote; Humans; Infections; loss‐of‐function variant; Male; Microtubule-Associated Proteins - genetics; Middle Aged; Multiplex Polymerase Chain Reaction - methods; Mutation; nexin‐dynein regulatory complex; Original; Patients; Population genetics; Populations; Primary ciliary dyskinesia; Recurrent infection; Signs and symptoms; sinopulmonary disease; Structure-function relationships; Tuberculosis; Ultrastructure; Japan; sinopulmonary disease; nexin-dynein regulatory complex; diffuse panbronchiolitis; primary ciliary dyskinesia; loss-of-function variant; founder mutation
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1033

Background Diffuse panbronchiolitis (DPB) is a sinopulmonary disease mainly affecting Asian populations. Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder impairing ciliary structure and function. These two disorders are not easily distinguished by clinical signs and symptoms. Methods In 105 Japanese patients with recurrent sinopulmonary infection, initially diagnosed with DPB, and 37 patients with recurrent airway infection diagnosed in adulthood, the deletion allele of DRC1 or CCDC164, recently recognized as a pathogenic PCD gene variant, was searched using a multiplexed PCR‐based method, and the deletion breakpoints and other variants around the gene were determined by Sanger sequencing and targeted resequencing. Results A large homozygous deletion in DRC1 was identified in three of the 142 patients. Furthermore, heterozygous carriers of the deletion with the same breakpoint were found with the allele frequency of 0.002 in the healthy Japanese population, indicating that this loss‐of‐function variant may be acting as a common mutation causing PCD in Japanese. Conclusion PCD caused by the DRC1 defect is not readily identified by either high‐speed video‐microscopy or ciliary ultrastructure analysis, posing significant difficulties in reaching a correct diagnosis without the aid of genetic tests. Careful investigation of the causes of sinopulmonary diseases is warranted in Asian populations. A large homozygous deletion in DRC1 was identified in three patients with recurrent sinopulmonary infection. Furthermore, heterozygous carriers of the DRC1 deletion with the same break point were found with the allele frequency of 0.002 in the healthy Japanese population, indicating that this loss‐of‐function variant may be acting as a common mutation causing PCD in Japanese.