Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study

IF 4.6 2区 医学 Q1 RESPIRATORY SYSTEM
Lung Pub Date : 2024-04-11 DOI:10.1007/s00408-024-00696-0
Noelia Rodriguez Mier, Martine Jaspers, Evelien Van Hoof, Mark Jorissen, Natalie Lorent, Marijke Proesmans, François Vermeulen, Jeroen Breckpot, Mieke Boon
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引用次数: 0

Abstract

Purpose

We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD).

Methods

We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes.

Results

We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were DNAH11 (n = 23) and DNAH5 (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p < 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between DNAH11 and DNAH5. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between DNAH11 and DNAH5 variants.

Conclusion

This study suggests a genotype–phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely DNAH11 and DNAH5.

Abstract Image

比利时单中心研究:原发性睫状肌运动障碍患者的基因谱和临床特征
目的我们旨在研究原发性睫状肌运动障碍(PCD)患者的临床特征与致病基因变异之间的相关性。方法我们对鲁汶大学医院随访的 PCD 患者进行了一项回顾性单中心研究。我们纳入了经基因证实的 PCD 患者,并描述了他们的基因型、睫状肌超微结构评估数据和临床特征。结果我们共收治了 74 名患者,中位年龄为 25.58 岁。最常涉及的基因是 DNAH11(23 个)和 DNAH5(19 个)。最常见的致病变异类型是错义变异(42 例)和框移变异(36 例),大多数患者为复合杂合变异(44 例)。DNAH11 和 DNAH5 的睫状体超微结构(p < 0.001)、位置(p = 0.015)和诊断年龄(中位数 9.50 岁 vs 4.71 岁,p = 0.037)存在差异。当校正坐位时,诊断年龄的差异不再显著(p = 0.973)。坐位不正的患者确诊时间更早(p = 0.031)。呼吸道微生物学(p = 0.161)、肺功能(横断面,p = 0.829;纵断面,p = 0.329)和胸部 CT 异常(p = 0.202)在 DNAH11 和 DNAH5 变体之间无显著差异。
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来源期刊
Lung
Lung 医学-呼吸系统
CiteScore
9.10
自引率
10.00%
发文量
95
审稿时长
6-12 weeks
期刊介绍: Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.
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