Submission Details

The WDR37 gene is located on chromosome 10 at 10p15.3 and encodes WD Repeat Domain 37, a member of the WD40 repeat-containing protein family, broadly involved in protein-protein interaction and molecular recognition in widespread biological processes. The specific function of WDR37 is unknown. WDR37 was first reported in relation to autosomal dominant neurooculocardiogenitourinary syndrome (NOCGUS) in 2019 (Reis et al., PMID:31327510 and Kanca et al., PMID:31327508). This multi-system disorder is characterized by severe complex ocular anomalies, dysmorphic craniofacial features, structural brain anomalies with severe neurological impairment, congenital heart defects, as well as skeletal (mostly spinal), genitourinary, and gastrointestinal anomalies, with feeding issues and poor growth. Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least 9 unique pathogenic/likely pathogenic variants (8 missense, 1 intronic deletion/splice) have been reported in 13 unrelated probands in five publications (PMIDs: 31327510, 31327508, 32530092, 34642815, 38044197) and are included in this curation. This gene-disease relationship is also supported by experimental evidence from protein-protein interaction data and model systems including drosophila, zebrafish, and mouse (PMIDs: 31327510, 31327508, 27626380). Functional studies are consistent with a dominant-negative mechanism of disease predominantly due to missense variants. In summary, there is definitive evidence to support relationship between WDR37 and neurooculocardiogenitourinary syndrome. No convincing contradictory evidence has emerged to date. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date October 18th, 2024 (SOP Version 11).