Petrarca Laura, Guida Valentina, Nenna Raffaella, De Luca Alessandro, Goldoni Marina, Bernardini Laura, Conti Maria Giulia, Cimino Giuseppe, Mancino Enrica, Masuelli Laura, Poli Piercarlo, Midulla Fabio
Maternal Infantile and Urological Sciences Department, "Sapienza" University of Rome.
Medical Genetics Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Pediatr Pulmonol. 2025 Apr;60(4):e71057. doi: 10.1002/ppul.71057.
Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by abnormalities in the motile cilia. Diagnosis could be hard to make, but genetic analysis could be important for the diagnosis and for defining prognosis.
To evaluate the clinical, ultrastructural, and molecular characteristics of a cohort of PCD subjects.
The study cohort included PCD patients enrolled in two Italian centers. Clinical data were retrospectively collected consulting medical records. All patients underwent nasal brushing and peripheral blood sampling for ultrastructural analysis of motile cilia and genetic testing, respectively.
A total of 39 patients with PCD were enrolled (median age 25.5 years, range 2.5-54.3 years). All patients showed common clinical features, which included SIT in 22/39 (56.4%), chronic rhinitis in 31/39 (79.5%), chronic sinusitis in 26/37 (66.7%), chronic cough in 32/39 (82.1%), and neonatal respiratory distress in 46.2% (18/39). The genetic defect was identified in 27/39 patients (69.2%), while a diagnostic ultrastructure was found in 27/35 (77.1%). Assessing genotype-phenotype correlations, subjects with biallelic pathogenic variants in CCDC39 and CCDC40 genes had a significantly lower forced expiratory volume in the first second of exhalation value (p = 0.017) than subjects with pathogenic variants in DNAH5 or in other PCD-related genes.
Our study further highlights the high heterogeneity of ultrastructural defects and genetics characterizing patients with PCD, as well as providing additional evidence that patients with biallelic pathogenic variants in CCDC39 or CCDC40 display a worse clinical phenotype than patients with pathogenic variants in other PCD genes.
原发性纤毛运动障碍（PCD）是一种罕见的遗传性疾病，其特征是运动性纤毛异常。诊断可能具有挑战性，但基因分析对于诊断和确定预后可能很重要。
评估一组PCD患者的临床、超微结构和分子特征。
研究队列包括在两个意大利中心登记的PCD患者。通过查阅病历回顾性收集临床数据。所有患者均接受鼻拭子检查和外周血采样，分别用于运动性纤毛的超微结构分析和基因检测。
共纳入39例PCD患者（中位年龄25.5岁，范围2.5 - 54.3岁）。所有患者均表现出常见的临床特征，其中22/39（56.4%）有鼻窦炎，31/39（79.5%）有慢性鼻炎，26/37（66.7%）有慢性鼻窦炎，32/39（82.1%）有慢性咳嗽，46.2%（18/39）有新生儿呼吸窘迫。27/39例患者（69.2%）鉴定出基因缺陷，27/35例（77.1%）发现诊断性超微结构。评估基因型 - 表型相关性时，CCDC39和CCDC40基因双等位基因致病性变异的患者第一秒用力呼气量值显著低于DNAH5或其他PCD相关基因致病性变异的患者（p = 0.017）。
我们的研究进一步强调了PCD患者超微结构缺陷和遗传学的高度异质性，同时提供了额外证据，即CCDC39或CCDC40基因双等位基因致病性变异的患者比其他PCD基因致病性变异的患者表现出更差的临床表型。
