Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Anim Genet. 2023 Jun;54(3):412-415. doi: 10.1111/age.13306. Epub 2023 Feb 14.
Primary ciliary dyskinesia (PCD) represents a group of diseases characterized by impaired movement of cilia and subsequent health problems in diverse organ systems, notably the respiratory tract. Almost 50 candidate genes for PCD are known in humans. In this study, we investigated an Australian Shepherd dog with a history of recurrent respiratory infections and nasal discharge. A transmission electron microscopy investigation led to the diagnosis of PCD with central pair defect, in which the normal 9:2 arrangement of respiratory cilia was altered and reduced to a 9:0 arrangement. Whole genome sequencing data from the affected dog was obtained and searched for variants in PCD candidate genes that were not present in 918 control genomes from different breeds. This revealed a homozygous single base pair exchange at a splice site of STK36, XM_038585732.1:c.2868-1G>A. The mutant allele was absent from 281 additionally genotyped Australian Shepherd dogs. RT-PCR confirmed aberrant splicing in the affected dog with the skipping of exon 20 and the insertion of a cryptic exon, which is predicted to lead to a premature stop codon and truncation of 36% of the STK36 wild-type open reading frame, XP_038441660.1:(p.Met957Profs*11). STK36 variants were previously reported to cause PCD in humans and mice. The knowledge from other species together with the absence of the mutant allele in more than 1000 control dogs suggests STK36:c.2868-1G>A as the most likely candidate variant for PCD in the investigated case.
原发性纤毛运动障碍（PCD）是一组以纤毛运动障碍为特征的疾病，随后会导致呼吸道等多种器官系统出现健康问题。目前已知人类有近 50 个 PCD 的候选基因。本研究调查了一只具有复发性呼吸道感染和鼻分泌物病史的澳大利亚牧羊犬。电镜检查提示中央对缺陷型 PCD，其中正常的呼吸纤毛 9:2 排列改变，减少到 9:0 排列。对受影响的犬进行全基因组测序，并在未在来自不同品种的 918 个对照基因组中发现的 PCD 候选基因中搜索变体。结果发现 STK36 的一个剪接位点发生了纯合单碱基对交换，XM_038585732.1:c.2868-1G>A。该突变等位基因在 281 只额外的澳大利亚牧羊犬中不存在。RT-PCR 证实受影响的犬存在异常剪接，第 20 外显子缺失，并插入一个隐匿外显子，预计会导致提前终止密码子，以及 STK36 野生型开放阅读框的 36%截断，XP_038441660.1:(p.Met957Profs*11)。STK36 变体以前被报道在人类和小鼠中引起 PCD。其他物种的知识以及在 1000 多个对照犬中未发现突变等位基因表明，STK36:c.2868-1G>A 是所研究病例中 PCD 的最可能候选变体。
