Skeletal dysplasia
Gene: DLL4
Adams-Oliver listed in brachydactylies (with extraskeletal manifestations) gp of SD. Several cases reported.; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adams-Oliver syndrome 6, 616589
Publications
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: DLL4; Initial rating suggestion: greenCreated: 6 Mar 2019, 11:36 a.m.
Meester et al PMID: 26299364 using candidate gene approach identified 9 heterozygous mutations in DLL4 (which is a NOTCH ligand) from 91 families - same pathway as other genes previously idetified to cause Adams Oliver syndrome.
No functional studies were performed, but software predicted pathogenicity of missense mutations.
Evidence of non penetrance in the paper - affected siblings inheriting mutation from seemingly unaffected parent.
Sources: OtherCreated: 10 Sep 2018, 3:40 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adams-Oliver syndrome 6 616589
Publications
Added phenotypes Adams-Oliver syndrome 6, 616589 for gene: DLL4
Source NHS GMS was added to DLL4. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for gene: DLL4 were changed from Adams-Oliver syndrome 6 616589 to Adams-Oliver syndrome 6, 616589
Publications for gene: DLL4 were set to PMID: 26299364
Gene: dll4 has been classified as Green List (High Evidence).
gene: DLL4 was added gene: DLL4 was added to Unexplained skeletal dysplasia. Sources: Other Mode of inheritance for gene: DLL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DLL4 were set to PMID: 26299364 Phenotypes for gene: DLL4 were set to Adams-Oliver syndrome 6 616589 Penetrance for gene: DLL4 were set to Incomplete Review for gene: DLL4 was set to GREEN