Expanding the phenotypic spectrum consequent upon de novo WDR37 missense variants.

Abstract

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.

• Authors: Eleanor Hay, Robert H Henderson, Sahar Mansour, Charu Deshpande, Rachel Jones, Savita Nutan, Kshitij Mankad, Rodrigo M Young, Mariya Moosajee, Genomics England Research Consortium, Gavin Arno
• Journal: Clinical genetics (Clin Genet) Vol. 98 Issue 2 Pg. 191-197 (08 2020) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 32530092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.

Chemical References

• Nuclear Proteins
• WDR37 protein, human

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Coloboma (complications, genetics, pathology)
• Epilepsy (complications, genetics, pathology)
• Eye Diseases (complications, genetics, pathology)
• Female
• Humans
• Infant
• Infant, Newborn
• Intellectual Disability (complications, genetics, pathology)
• Male
• Musculoskeletal Abnormalities (complications, genetics, pathology)
• Mutation (genetics)
• Mutation, Missense (genetics)
• Nuclear Proteins (genetics)
• Phenotype
• Young Adult