Expanding the phenotypic spectrum consequent upon de novo WDR37 missense variants.
Structural eye disorders are increasingly recognised as having a genetic basis, although current genetic testing is limited in its success. De novo missense variants in WDR37 are a recently described cause of a multisystemic syndromic disorder featuring ocular coloboma. This study characterises the phenotypic spectrum of this disorder and reports 2 de novo heterozygous variants (p.Thr115Ile, p.Ser119Tyr) in three unrelated Caucasian individuals. All had a clinical phenotype consisting of bilateral iris and retinal coloboma, developmental delay and additional, variable multisystem features. The variants fall within a highly conserved region upstream of the WD-repeat domains, within an apparent mutation cluster. Consistent with the literature, intellectual disability, structural eye disorders, epilepsy, congenital heart disease, genitorenal anomalies and dysmorphic facial features were observed. In addition, a broader developmental profile is reported with a more specific musculoskeletal phenotype described in association with the novel variant (p.Thr115Ile). We further expand the phenotypic spectrum of WDR37-related disorders to include those with milder developmental delay and strengthen the association of ocular coloboma and musculoskeletal features. We promote the inclusion of WDR37 on gene panels for intellectual disability, epilepsy and structural eye disorders.
['Hay|Eleanor|E|', 'Henderson|Robert H|RH|', 'Mansour|Sahar|S|', 'Deshpande|Charu|C|', 'Jones|Rachel|R|', 'Nutan|Savita|S|', 'Mankad|Kshitij|K|', 'Young|Rodrigo M|RM|', 'Moosajee|Mariya|M|', 'Research Consortium|Genomics England|GE|', 'Arno|Gavin|G|0000-0002-6165-7888']
D000293:Adolescent D000328:Adult D002648:Child D002675:Child, Preschool D003103:Coloboma D004827:Epilepsy D005128:Eye Diseases D005260:Female D006801:Humans D007223:Infant D007231:Infant, Newborn D008607:Intellectual Disability D008297:Male D009139:Musculoskeletal Abnormalities D009154:Mutation D020125:Mutation, Missense D009687:Nuclear Proteins D010641:Phenotype D055815:Young Adult
coloboma developmental anterior segment disease molecular genetics