Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia
Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia
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DOI：
10.1183/09031936.00052014
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发表时间：
2014-12-01
影响因子：
24.3
通讯作者：
Werner, Claudius
中科院分区：
文献类型：
--
作者：
Raidt, Johanna;Wallmeier, Julia;Werner, Claudius
原发性纤毛运动障碍（PCD）是一种罕见的遗传性疾病，导致反复呼吸道感染。睫状体跳动的高速视频显微镜分析（HVMA）目前是大多数中心PCD的一线诊断工具，具有挑战性，因为最近的研究已经将PCD中HVMA发现的范围从严重异常扩展到非常微妙。本研究的目的是描述遗传学证实的PCD个体中HVMA发现的多样性。HVMA是疑似PCD个体常规检查的一部分。随后的分子分析确定了66个个体PCD相关基因的双等位基因突变。在17个基因中发现了双等位基因突变（19个新突变）：DNAI 1、DNAI 2、DNAH 5、DNAH 11、CCDC 103、ARMC 4、KTU/DNAAF 2、LRRC 50/DNAAF 1、LRRC 6、DYX 1C 1、ZMYND 10、CCDC 39、CCDC 40、CCDC 164、HYDIN、RSPH 4A和RSPH 1。睫状体搏动模式的变化与遗传学发现相关性很好，允许对不同遗传组的典型HVMA发现进行分类。相比之下，睫状体搏动频率的分析并没有导致额外的诊断impact.In结论，这项研究提供了详细的知识的多样性HVMA的发现在PCD，因此可以被看作是一个指南，以改善PCD的诊断。
Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections. High-speed video-microscopy analysis (HVMA) of ciliary beating, currently the first-line diagnostic tool for PCD in most centres, is challenging because recent studies have expanded the spectrum of HVMA findings in PCD from grossly abnormal to very subtle. The objective of this study was to describe the diversity of HVMA findings in genetically confirmed PCD individuals.HVMA was performed as part of the routine work-up of individuals with suspected PCD. Subsequent molecular analysis identified biallelic mutations in the PCD-related genes of 66 individuals. 1072 videos of these subjects were assessed for correlation with the genotype.Biallelic mutations (19 novel) were found in 17 genes: DNAI1, DNAI2, DNAH5, DNAH11, CCDC103, ARMC4, KTU/DNAAF2, LRRC50/DNAAF1, LRRC6, DYX1C1, ZMYND10, CCDC39, CCDC40, CCDC164, HYDIN, RSPH4A and RSPH1. Ciliary beat pattern variations correlated well with the genetic findings, allowing the classification of typical HVMA findings for different genetic groups. In contrast, analysis of ciliary beat frequency did not result in additional diagnostic impact.In conclusion, this study provides detailed knowledge about the diversity of HVMA findings in PCD and may therefore be seen as a guide to the improvement of PCD diagnostics.