Respiratory ciliopathies including non-CF bronchiectasis

Gene: BRWD1

Red List (low evidence)

As reviewed by Ivone Leong below, biallelic BRWD1 variants have been reported in three unrelated patients displaying PCD-like phenotype including recurring airway infections, bronchiectasis and rhinosinusitis. This gene is now associated with relevant phenotype in OMIM (MIM #620438).

However, the association of BRWD1 gene with primary ciliary dyskinesia (MONDO:0016575) has been classified as 'Disputed' by the Motile Ciliopathy expert panel in ClinGen. Detailed information on this classification can be found in https://search.clinicalgenome.org/CCID:004289.

The reason for their classification is as follows:
"Individuals with variants in BRWD1 and clinical features of PCD are reported in the literature. However, no functional data support the pathogenicity of the variants and their association with PCD. No valid experimental evidence remains to support this curation."

Created: 14 Jul 2025, 4:02 p.m. | Last Modified: 17 Jul 2025, 4:49 p.m.

Panel Version: 4.43

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 51, OMIM:620438

Publications

• 33389130

Red List (low evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Created: 31 Jan 2023, 1:31 p.m. | Last Modified: 31 Jan 2023, 1:31 p.m.

Panel Version: 2.3

Green List (high evidence)

This gene is not associated with a phenotype in OMIM or Gene2Phenotype. This gene was added to the Laterality disorders and isomerism (Version 1.44) panel by Zornitza Stark with the following review:

"Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-like" symptoms of reccurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls). Sources: Literature
Zornitza Stark (Australian Genomics), 7 Feb 2021"

After discussion with the Genomics England Clinical Team it was decided that this gene was better suited to this panel.
Sources: Literature

Created: 4 May 2021, 10:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia, asthenoteratozoospermia

Publications

• 33389130