Activity
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6 actions
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| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 | WDR44 | Seb Lunke Marked gene: WDR44 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 | WDR44 | Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 | WDR44 | Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 | WDR44 | Seb Lunke Classified gene: WDR44 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 | WDR44 | Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 | WDR44 |
Andrew Fennell gene: WDR44 was added gene: WDR44 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. 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 Added comment: 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. 3 patients had renal anomalies including 1 with unilateral cystic kidney disease; and nephritis, and kidney hypoplasia resulting in renal failure in two patients. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, 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 |
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