Biallelic DAW1 variants cause a motile ciliopathy characterized by laterality defects and subtle ciliary beating abnormalities.

ABSTRACT:

Purpose

The clinical spectrum of motile ciliopathies includes laterality defects, hydrocephalus, and infertility as well as primary ciliary dyskinesia when impaired mucociliary clearance results in otosinopulmonary disease. Importantly, approximately 30% of patients with primary ciliary dyskinesia lack a genetic diagnosis.

Methods

Clinical, genomic, biochemical, and functional studies were performed alongside in vivo modeling of DAW1 variants.

Results

In this study, we identified biallelic DAW1 variants associated with laterality defects and respiratory symptoms compatible with motile cilia dysfunction. In early mouse embryos, we showed that Daw1 expression is limited to distal, motile ciliated cells of the node, consistent with a role in left-right patterning. daw1 m

SUBMITTER: Leslie JS 

PROVIDER: S-EPMC10584193 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature