Work

Case Report: Minigene assays reveal a novel DNAAF6 intronic variant as the key etiology for primary ciliary dyskinesia

Year: 2025

Type: article

Abstract: Background Primary ciliary dyskinesia (PCD), a rare hereditary disorder characterized by impaired ciliary motility, is frequently linked to infertility. Elucidating PCD’s genetic basis is critical for accurate diagnosis and clinical management. However, research on the pathogenicity of intronic variants in non-classical splice regions of DNAAF6 —a newly identified PCD-associated gene in recent years—remains scarce. Case presentation A proband with primary ciliary dyskinesia (PCD) and male infertility underwent whole exome sequencing (WES), revealing a novel hemizygous intronic variant in the DNAAF6 gene (NM_173494.2: c.515 + 3_515+6del, Clinvar Variation ID:4075425). Sanger sequencing confirmed this variant in his affected brother. A minigene splicing assay showed that the variant caused exon six skipping, leading to a frameshift. Transmission electron microscopy (TEM) analysis of sperm flagella indicated absent outer and inner dynein arms, resulting in flagellar immotility. Conclusion This study identifies and confirms a novel pathogenic intronic variant of DNAAF6 in a Chinese PCD family, expanding the DNAAF6 mutational spectrum. It also emphasizes the critical role of minigene-based functional validation in interpreting variants of uncertain significance (VUS).

Source: Frontiers in Genetics

DOI: 10.3389/fgene.2025.1692658

Authors: Yupeng Long, Huixian Li, Haoyue Yu, Qian Yi, Xiong Meng, Xi Wang, Qinqin Ren, Dongyan Ding, Haidong Li, Fenglan Zhang, Hao Qiu, Xuemei Yang

Institutions: Army Medical University, Chinese People's Liberation Army, Dian Diagnostics (China)

Language: English

Topic: Cystic Fibrosis Research Advances

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801