A case of primary ciliary dyskinesis with DRC1 deletion and literature review: Additional evidence on the founder effect

Pediatr Int. 2024 Jan-Dec;66(1):e15808. doi: 10.1111/ped.15808.

Abstract

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.

Keywords: DRC1; Japanese; Korean; primary ciliary dyskinesia.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Exome Sequencing
  • Exons / genetics
  • Female
  • Founder Effect*
  • Humans
  • Kartagener Syndrome / diagnosis
  • Kartagener Syndrome / genetics