Barber Andrew T, Davis Stephanie D, Ferkol Thomas W, Shapiro Adam J, Atkinson Jeff, Sagel Scott D, Dell Sharon D, Olivier Kenneth, Milla Carlos, Rosenfeld Margaret, Li Lang, Lin Feng-Chang, Sullivan Kelli M, Capps Nicole A, Zariwala Maimoona A, Knowles Michael R, Leigh Margaret W
Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Pediatr Pulmonol. 2025 May;60(5):e71091. doi: 10.1002/ppul.71091.
To evaluate the relationship between ciliary ultrastructure/genotype and prevalence of neonatal respiratory distress (NRD) in primary ciliary dyskinesia (PCD).
This was a retrospective analysis from a multicenter, prospective study of children and adults with PCD. Participants were classified by ultrastructural defect associated with their diagnostic genetic variants: 1) outer dynein arm defect alone (ODA), 2) outer plus inner dynein arm defect (ODA/IDA), 3) inner dynein arm defect with microtubular disorganization (IDA/MTD), 4) DNAH11 (encodes ODA protein but has normal ultrastructure), and 5) normal/near-normal/other. The likelihood of NRD between ultrastructure groups or genotypes was evaluated by multivariate analysis using logistic regression, controlled for age, gender, race, and variant type. Similar analysis was performed within individual genotypes to assess association of NRD with the presence of 2 loss-of-function variants.
Of the 455 participants analyzed, 305 (67.0%) reported NRD. The odds ratio for NRD in the DNAH11 group was significantly lower (OR: 0.35, 95% CI: 0.16-0.76) compared to NRD in the ODA group. Within the DNAH5 group, those with two loss-of-function variants were more likely to have NRD compared to those with possible residual function variants (OR: 3.06, 95% CI: 1.33-7).
NRD is less common in those with DNAH11 variants, thus a high index of suspicion should remain for PCD in the absence of NRD. Variant type (loss-of-function vs. residual function) may explain phenotypic variability within individual PCD genes.
评估原发性纤毛运动障碍（PCD）中纤毛超微结构/基因型与新生儿呼吸窘迫（NRD）患病率之间的关系。
这是一项对患有PCD的儿童和成人进行的多中心前瞻性研究的回顾性分析。参与者根据与其诊断性基因变异相关的超微结构缺陷进行分类：1）单纯外动力臂缺陷（ODA），2）外动力臂加内动力臂缺陷（ODA/IDA），3）伴有微管紊乱的内动力臂缺陷（IDA/MTD），4）DNAH11（编码ODA蛋白但超微结构正常），以及5）正常/接近正常/其他。使用逻辑回归进行多变量分析，在控制年龄、性别、种族和变异类型的情况下，评估超微结构组或基因型之间NRD的可能性。在个体基因型内进行类似分析，以评估NRD与两个功能丧失变异的存在之间的关联。
在分析的455名参与者中，305名（67.0%）报告有NRD。与ODA组中的NRD相比，DNAH11组中NRD的优势比显著更低（OR：0.35，95%CI：0.16 - 0.76）。在DNAH5组中，与可能具有残余功能变异的个体相比，具有两个功能丧失变异的个体更有可能发生NRD（OR：3.06，95%CI：1.33 - 7）。
DNAH11变异个体中NRD较少见，因此在无NRD的情况下，对PCD仍应保持高度怀疑。变异类型（功能丧失与残余功能）可能解释个体PCD基因内的表型变异性。
