Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
J Hum Genet. 2023 Jun;68(6):369-374. doi: 10.1038/s10038-023-01122-8. Epub 2023 Feb 7.
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting ciliary structure and function. PCD exhibiting dynein regulatory complex subunit 1 (DRC1) exon 1-4 deletion has been reported in several Japanese PCD patients; however, no large scale studies have been performed. Here, we aimed to determine the prevalence and founder effect of this variant in the Korean population. Using an in-house copy number variation tool, we screened for DRC1 exon 1-4 deletion in 20 patients with PCD and exome data of 1435 patients in the Seoul National University Hospital repository. In cases of suspected DRC1 deletion, confirmatory gap-PCR was performed. In a PCD cohort, three of 20 (15%) patients were positive for DRC1 exon 1-4 deletion (NM_145038.5(DRC1): c.1-3952_540 + 1331del27748-bp) while pathogenic variants were found in CCDC39 (N = 1), DNAAF6 (N = 1), DNAH9 (N = 1). In the 1,435-sample exome data, seven patients (0.49%) were confirmed to have DRC1 exon 1-4 deletion. A chimeric sequence including the junction was searched from the 1000 Genomes Project data repository. One Japanese patient (0.96%) was found to have the same DRC1 exon 1-4 deletion, which was absent in other populations. This study demonstrated that the DRC1 exon 1-4 deletion is a founder mutation based on haplotype analysis. In summary, the prevalence of PCD based on DRC1 exon 1-4 deletion is particularly high in Korean and Japanese populations, which is attributed to the founder effect. Genetic testing for DRC1 exon 1-4 deletion should be considered as an initial screening tool for Korean and Japanese patients with PCD.
原发性纤毛运动障碍（PCD）是一种遗传性异质性疾病，影响纤毛的结构和功能。已经在一些日本 PCD 患者中报道了表现出动力蛋白调节复合物亚基 1（DRC1）外显子 1-4 缺失的 PCD；然而，尚未进行大规模研究。在这里，我们旨在确定该变体在韩国人群中的流行率和创始人效应。使用内部拷贝数变异工具，我们对 20 名 PCD 患者进行了 DRC1 外显子 1-4 缺失的筛查，并对首尔国立大学医院存储库中的 1435 名患者的外显子数据进行了筛查。在疑似 DRC1 缺失的情况下，进行了确认性缺口-PCR。在 PCD 队列中，20 名患者中有 3 名（15%）患者的 DRC1 外显子 1-4 缺失阳性（NM_145038.5(DRC1)：c.1-3952_540+1331del27748-bp），而致病性变异存在于 CCDC39（N=1）、DNAAF6（N=1）、DNAH9（N=1）中。在 1435 个样本外显子数据中，有 7 名患者（0.49%）被证实存在 DRC1 外显子 1-4 缺失。从 1000 基因组计划数据存储库中搜索包含接头的嵌合序列。在一名日本患者（0.96%）中发现了相同的 DRC1 外显子 1-4 缺失，而在其他人群中则不存在。这项研究表明，基于单倍型分析，DRC1 外显子 1-4 缺失是一种创始突变。总之，基于 DRC1 外显子 1-4 缺失的 PCD 患病率在韩国和日本人群中特别高，这归因于创始效应。对于韩国和日本的 PCD 患者，应考虑将 DRC1 外显子 1-4 缺失的基因检测作为初始筛查工具。
