原发性纤毛运动障碍伴 DRC1 缺失 1 例及文献复习：关于 founder 效应的更多证据。
A case of primary ciliary dyskinesis with DRC1 deletion and literature review: Additional evidence on the founder effect.
机构信息
Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Royal College of Surgeons in Ireland, Dublin, Ireland.
出版信息
Pediatr Int. 2024 Jan-Dec;66(1):e15808. doi: 10.1111/ped.15808.
BACKGROUND
Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by defects in various genes affecting ciliary function. It is currently unclear why DRC1 gene variants are a relatively frequent cause of disease in Japanese and Korean patients.
METHODS
A 12-year-old Japanese girl with bronchiectasis was suspected of PCD and examined using whole-exome sequencing (WES). The breakpoint region was confirmed by Sanger sequencing and evaluation of transposable elements.
RESULTS
Whole-exome sequencing revealed a deletion of DRC1 exons 1-4 in the patient, followed by validation with Sanger sequencing. A DRC1 exon 1-4 deletion is recurrently observed in Japanese and Korean patients with PCD. All reported patients carry the same breakpoint region, which shows signs of Alu-mediated recombination. Intriguingly, common haplotypes were observed around the DRC1 gene in Japanese and Korean patients.
CONCLUSION
The recurrent DRC1 exon 1-4 deletion is therefore likely to be a founder variant and should be considered a major genetic cause of PCD in Japanese and Korean patients with PCD.
背景
原发性纤毛运动障碍（PCD）是一种罕见的遗传性疾病，由影响纤毛功能的各种基因缺陷引起。目前尚不清楚为什么 DRC1 基因突变是日本和韩国患者疾病的相对常见原因。
方法
一名 12 岁的日本支气管扩张女孩疑似患有 PCD，并接受了全外显子组测序（WES）检查。通过 Sanger 测序和转座元件评估确认了断点区域。
结果
全外显子组测序显示患者存在 DRC1 外显子 1-4 的缺失，随后通过 Sanger 测序进行了验证。在日本和韩国的 PCD 患者中，经常观察到 DRC1 外显子 1-4 的缺失。所有报道的患者携带相同的断点区域，显示出 Alu 介导重组的迹象。有趣的是，在日本和韩国的 PCD 患者中，DRC1 基因周围观察到常见的单倍型。
结论
因此，反复出现的 DRC1 外显子 1-4 缺失很可能是一个创始变体，应该被认为是日本和韩国 PCD 患者 PCD 的主要遗传原因。
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