Targeted gene(s)/phenotype under study
- Gene: DCAF15
- OMIM # or ORPHA code: This gene has no registration with OMIM/ ORPHA
- Phenotype: The phenotype of the 3 patients identified so far is very similar and includes common dysmorphic facial features, severe neurodevelopmental delay, arthrogryposis, congenital CNS malformations, visual impairment and hearing loss, among others.
- Disorder under study: syndromic neurodevelopmental disorder.
Abstract
We have a cohort of 3 patients with a similar syndromic neurodevelopmental disorder and the same variant in DCAF15 gene. This is a variant without allelic frequency described in gnomAD and with constraint metrics that indicate that it might be intolerant to protein-truncating and missense variations. Dcaf15 gene expression data in mice tissues show a ubiquitous expression pattern, which might be compatible with a malformative syndrome. This gene is a substrate-recognition component of a cullin-4-RING E3 ubiquitin-protein ligase complex that possibly mediates ubiquitination and degradation of cohesin subunits SMC1A and SMC3.
The phenotype of the 3 patients identified so far is very similar and includes common dysmorphic facial features, severe neurodevelopmental delay, arthrogryposis, congenital CNS malformations, visual impairment and hearing loss, among others.
In all three cases the presumptive diagnosis was similar and all of them had previous extensive genetic studies with normal result, being the variant in this gene the only candidate.
Coordinating clinicians /researchers
- Dr. Sixto García-Miñaúr
- Dr. Antonio Vitobello
- Dr. María Palomares
Contact:
Institution
INGEMM, Institute of Medical and Molecular Genetics
Hospital Universitario La Paz
Madrid-Spain
Centre Hospitalier Universitaire Dijon Bourgogne
Inserm 1231 GAD team
Dijon, France
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples : No
- Resampling of patients : No
- Linked to a translational/basic research project? Yes