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Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia
BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252271/ https://www.ncbi.nlm.nih.gov/pubmed/34210339 http://dx.doi.org/10.1186/s13023-021-01840-2 |
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author | Zhao, Xinyue Bian, Chun Liu, Keqiang Xu, Wenshuai Liu, Yaping Tian, Xinlun Bai, Jing Xu, Kai-Feng Zhang, Xue |
author_facet | Zhao, Xinyue Bian, Chun Liu, Keqiang Xu, Wenshuai Liu, Yaping Tian, Xinlun Bai, Jing Xu, Kai-Feng Zhang, Xue |
author_sort | Zhao, Xinyue |
collection | PubMed |
description | BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations. RESULTS: A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups. CONCLUSION: This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-01840-2. |
format | Online Article Text |
id | pubmed-8252271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82522712021-07-06 Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia Zhao, Xinyue Bian, Chun Liu, Keqiang Xu, Wenshuai Liu, Yaping Tian, Xinlun Bai, Jing Xu, Kai-Feng Zhang, Xue Orphanet J Rare Dis Research BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations. RESULTS: A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups. CONCLUSION: This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-01840-2. BioMed Central 2021-07-01 /pmc/articles/PMC8252271/ /pubmed/34210339 http://dx.doi.org/10.1186/s13023-021-01840-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhao, Xinyue Bian, Chun Liu, Keqiang Xu, Wenshuai Liu, Yaping Tian, Xinlun Bai, Jing Xu, Kai-Feng Zhang, Xue Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title | Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title_full | Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title_fullStr | Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title_full_unstemmed | Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title_short | Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia |
title_sort | clinical characteristics and genetic spectrum of 26 individuals of chinese origin with primary ciliary dyskinesia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252271/ https://www.ncbi.nlm.nih.gov/pubmed/34210339 http://dx.doi.org/10.1186/s13023-021-01840-2 |
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