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Mendeliome

Gene: WDR44

Green List (high evidence)

WDR44 (WD repeat domain 44)
EnsemblGeneIds (GRCh38): ENSG00000131725
EnsemblGeneIds (GRCh37): ENSG00000131725
WDR44 is in 5 panels

2 reviews

Seb Lunke (Victorian Clinical Genetics Services)

Comment when marking as ready: GoF mentioned but not well established.
Created: 1 Feb 2024, 12:37 a.m. | Last Modified: 1 Feb 2024, 12:37 a.m.
Panel Version: 1.1507

Andrew Fennell (Monash Genetics)

Green List (high evidence)

11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Created: 1 Feb 2024, 12:36 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Ciliopathy, MONDO:0005308, WDR44-related

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
Phenotypes
  • Ciliopathy, MONDO:0005308, WDR44-related
Clinvar variants
Variants in WDR44
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Feb 2024, Gel status: 3

Entity classified by Genomics England curator

Seb Lunke (Victorian Clinical Genetics Services)

Gene: wdr44 has been classified as Green List (High Evidence).

1 Feb 2024, Gel status: 3

Entity classified by Genomics England curator

Seb Lunke (Victorian Clinical Genetics Services)

Gene: wdr44 has been classified as Green List (High Evidence).

1 Feb 2024, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Andrew Fennell (Monash Genetics)

gene: WDR44 was added gene: WDR44 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: WDR44 were set to PMID: 38191484 Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related Review for gene: WDR44 was set to GREEN