Genetic epilepsy syndromes
Gene: DENND5A
AR EIEE 49 - Onset of seizures in the neonatal period. Han et al, 2016 - 4 children from 2 unrelated consang families (Saudi and Jordian descent) - hom fs mutations identified - segregated with disease in the families, no functional work done, however knockdown of Dennd5a in cultured neuronal cells done. Anazi et al, 2017 - 2 unrelated girls each born of consang parents - intractable seizures in first few days of life - hom variants - 1 missense, 1 fs.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
pileptic encephalopathy early infantile, 617281
Publications
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Amber to Green: Although only Probable confidence level in DD-G2P for EPILEPTIC ENCEPHALOPATHY, there are suffcient cases from PMIDs 27866705 and 27431290 (5 individuals from 4 unrelated families) to support gene:disease association and diagnostic rating.Created: 22 Nov 2018, 2:53 p.m.
In 3 patients from 2 unrelated consanguineous families (from Saudi Arabia and Jordan) with early infantile epileptic encephalopathy-49, Han et al. (2016, PMID:27866705) identified homozygous frameshift mutations in the DENND5A gene (c.517_518delGA, resulting in a frameshift and premature termination Asp173ProfsTer8 and c.2547delG resulting in a frameshift and premature termination Lys850SerfsTer11).
In 2 unrelated girls, each born of consanguineous parents, with EIEE49, Anazi et al. (2017, PMID:27431290) identified homozygous mutations in the DENND5A gene (c.1622A-G, NM_015213.3, D541G).Created: 22 Nov 2018, 2:48 p.m.
5 patients from 4 unrelated families reported with bi-allelic variants in this gene and epileptic encephalopathy.Created: 12 Aug 2018, 6:34 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epileptic encephalopathy, early infantile, 49, MIM#617281
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to DENND5A.
Source NHS GMS was added to DENND5A.
Zornitza Stark: 5 patients from 4 unrelated fa
Gene: dennd5a has been classified as Green List (High Evidence).
Gene: dennd5a has been classified as Green List (High Evidence).
Gene: dennd5a has been classified as Amber List (Moderate Evidence).
Publications for gene: DENND5A were set to
Mode of inheritance for gene: DENND5A was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DENND5A were changed from to Epileptic encephalopathy, early infantile, 49, 617281
Expert Review Amber was added to DENND5A. Panel: Genetic Epilepsy Syndromes
DENND5A was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
DENND5A was created by Sarah Leigh