# Case Report: Identification of a novel hemizygous CFAP47 variant in a primary ciliary dyskinesia patient with dual ciliary and flagellar defects

## TL;DR

A new genetic variant in CFAP47 is linked to a rare disease affecting cilia and flagella, supporting its role in causing primary ciliary dyskinesia.

## Contribution

A novel hemizygous CFAP47 variant is identified as a likely cause of PCD with dual ciliary and flagellar defects.

## Key findings

- A hemizygous missense variant in CFAP47 was found in a PCD patient with ciliary and flagellar defects.
- The variant was associated with reduced CFAP47 mRNA levels in both patient sperm and an in vitro model.
- The findings expand the genetic spectrum of PCD and support CFAP47's role in the disease.

## Abstract

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous ciliopathy caused by structural and functional abnormalities of motile cilia. Although over 50 PCD-associated genes have been reported, the genetic spectrum remains incomplete. CFAP47, a gene linked to multiple morphological abnormalities of the flagella, has recently been implicated in PCD; however, further case studies are needed to strengthen this conclusion.

We investigated a male patient with suspected PCD who exhibited “9 + 2” ultrastructural abnormalities in both bronchial cilia and sperm flagella. Whole exome sequencing was performed to screen for pathogenic variants. The candidate variant was analyzed through bioinformatics tools, and CFAP47 expression levels were quantified via qPCR in both patient-derived sperm and an in vitro expression plasmid model.

Whole exome sequencing identified a hemizygous missense variant, CFAP47 (NM_001304548.2): c.3599T > A (p.Phe1200Tyr) in the patient. The pathogenicity of this variant was assessed through multiple in silico tools, with divergent predictions. Experimental validation revealed significantly decreased CFAP47 mRNA levels in the patient’s sperm and the HEK293 cells transfected with mutant plasmid compared to controls, suggesting impaired transcript stability.

Our study proposes a novel CFAP47 variant as a likely contributor to PCD, given its impact on mRNA expression. These findings strengthen the association between CFAP47 and PCD pathogenesis and expand the mutation spectrum of this emerging disease gene.