Fetal anomalies
Gene: DEPDC5Comment on list classification: Updated rating from Red to Amber inline with this recent Amber review by Rhiannon Mellis (GOSH), awaiting further evidence supporting that this gene can cause a fetal phenotype.Created: 19 Aug 2022, 3:21 p.m. | Last Modified: 19 Aug 2022, 3:21 p.m.
Panel Version: 1.930
This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).
Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.
Currently rated Green on the following other PanelApp panel(s): Intellectual disability, Genetics epilepsies. Amber on cortical malformations panel.
Details of review:
Previously reviewed as Red because only associated with familial epilepsy without structural brain anomalies (AD - caused by het LOF variants) but data presented by Dr Lara Menzies at CGS Spring Meeting 2021 suggests that there may also be a biallelic phenotype with hypomorphic variants. 5 cases presented from 3 unrelated Irish traveller families with significant polymicrogyria and macrocephaly as well as seizures and severe dev delay. At least 2 of the cases had prenatal features: ventriculomegaly, macrocephaly and IUGR for one, polymicrogyria on MRI for another - fetal MRI done because of FHx of affected child. (Unpublished data)
Liu et al 2020 (PMID: 32848577) report one case with homozygous missense variants in this gene, who had focal cortical dysplasia and seizures from 3yoCreated: 11 Aug 2022, 2:16 p.m. | Last Modified: 11 Aug 2022, 2:16 p.m.
Panel Version: 1.900
This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).
Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.
Currently rated Green on the following other PanelApp panel(s): Intellectual disability, Genetics epilepsies. Amber on cortical malformations panel.
Details of review:
Previously reviewed as Red because only associated with familial epilepsy without structural brain anomalies (AD - caused by het LOF variants) but data presented by Dr Lara Menzies at CGS Spring Meeting 2021 suggests that there may also be a biallelic phenotype with hypomorphic variants. 5 cases presented from 3 unrelated Irish traveller families with significant polymicrogyria and macrocephaly as well as seizures and severe dev delay. At least 2 of the cases had prenatal features: ventriculomegaly, macrocephaly and IUGR for one, polymicrogyria on MRI for another - fetal MRI done because of FHx of affected child. (Unpublished data)
Liu et al 2020 (PMID: 32848577) report one case with homozygous missense variants in this gene, who had focal cortical dysplasia and seizures from 3yoCreated: 11 Aug 2022, 2:16 p.m. | Last Modified: 11 Aug 2022, 2:16 p.m.
Panel Version: 1.900
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy; Structural brain malformations
Publications
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Epilepsy but no structural brain defects, so probably not detectable prenatally. Action taken: Demoted DEPDC5 gene rating from Green to Red.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCICreated: 11 Dec 2018, 9:04 a.m.
Gene: depdc5 has been classified as Amber List (Moderate Evidence).
Publications for gene: DEPDC5 were set to
Phenotypes for gene: DEPDC5 were changed from FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI to Epilepsy; Structural brain malformations
Mode of inheritance for gene: DEPDC5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Source Expert Review Red was added to DEPDC5. Rating Changed from Green List (high evidence) to Red List (low evidence)
gene: DEPDC5 was added gene: DEPDC5 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: DEPDC5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DEPDC5 were set to FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI