Interpreting Variants of Uncertain Significance in PCD: Abnormal Splicing Caused by a Missense Variant of DNAAF3.

ABSTRACT:

Background

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia. While approximately 50 genes have been identified, around 25% of PCD patients remain genetically unexplained; elucidating the pathogenicity of specific variants remains a challenge.

Methods

Whole exome sequencing (WES) and Sanger sequencing were conducted to identify potential pathogenic variants of PCD. Minigene assays were performed to evaluate the pathogenicity of variants. Transmission electron microscopy (TEM) and high-speed video analysis (HSVA) were conducted to analyze the function of cilia in respiratory epithelial cells.

Results

We identified two variants of DNAAF3: c.557G>A, p.G186E in exon 5, and c.1364G>A, p.G455D at the termina

SUBMITTER: Zheng H 

PROVIDER: S-EPMC11705539 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature