Research Foundation Of the University General Hospital of Valencia, Spain.
Am J Rhinol Allergy. 2012 Jul-Aug;26(4):260-4. doi: 10.2500/ajra.2012.26.3784.
Primary ciliary dyskinesia (PCD) is a congenital hereditary disease affecting 1/20,000-60,000 people that causes chronic sinusitis, bronchiectasis, sinus hypoplasia, secretory otitis media, and low fertility. The complexity and heterogeneity of the disease make diagnosis difficult. Although the genetic origin of PCD is clear, mutations in only five genes have been associated with the disease, and, to date, no disease-causing gene has been identified. Recently, low levels of AK7 gene expression have been linked to PCD. This study was designed to determine the mutational status of the AK7 gene in 31 PCD (17 PCD and 14 Kartagener syndrome diagnosed) patients compared with 40 healthy volunteers. We also determined the AK7 sequence in two families with members with PCD and investigated ciliary activity and ciliogenesis in one patient with a mutation in AK7.
We analyzed nasal mucociliary transport and cilial ultrastructure by electron microscopy and studied nasal ciliary beat frequency and beat pattern using high-resolution digital high speed video (DHSV) imaging. Mutation analyses were performed by direct resequencing of the 18 exons of the AK7 gene. Air-liquid interface differentiated cultures were studied using DHSV imaging and histochemistry. AK7 gene expression was studied by real-time reverse-transcription polymerase chain reaction.
We identified two mutations in the AK7 gene, the described single nucleotide polymorphism (rs2369679), and a new mutation (c.1214insT) that, to the best of our knowledge, has not been described previously. Family and functional studies indicated that c.1214insT could be related to PCD.
Our results indicate that AK7 may be involved in the development of PCD.
原发性纤毛运动障碍（PCD）是一种影响 1/20000-60000 人的先天性遗传性疾病，导致慢性鼻窦炎、支气管扩张、鼻窦发育不良、分泌性中耳炎和低生育力。该疾病的复杂性和异质性使得诊断困难。尽管 PCD 的遗传起源很明确，但仅与五种基因的突变有关，并且迄今为止尚未确定致病基因。最近，AK7 基因表达水平低与 PCD 有关。本研究旨在确定 31 例 PCD（17 例 PCD 和 14 例 Kartagener 综合征诊断）患者与 40 例健康志愿者相比 AK7 基因的突变状态。我们还在两个有 PCD 患者的家族中确定了 AK7 序列，并研究了一个 AK7 基因突变患者的纤毛活动和纤毛发生。
我们通过电子显微镜分析了鼻黏液纤毛输送和纤毛超微结构，并使用高分辨率数字高速视频（DHSV）成像研究了鼻纤毛拍打频率和拍打模式。通过直接对 AK7 基因的 18 个外显子进行重测序进行突变分析。使用 DHSV 成像和组织化学研究了气液界面分化培养。通过实时逆转录聚合酶链反应研究 AK7 基因表达。
我们在 AK7 基因中发现了两个突变，一个是已描述的单核苷酸多态性（rs2369679），另一个是新的突变（c.1214insT），据我们所知，该突变以前尚未描述过。家族和功能研究表明，c.1214insT 可能与 PCD 有关。
我们的结果表明，AK7 可能参与 PCD 的发生。
