Early onset or syndromic epilepsy

Gene: DENND5A

Green List (high evidence)

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

• 27866705
• 27431290

I don't know

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.

Green List (high evidence)

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

• 27431290, 27866705

Variants in this GENE are reported as part of current diagnostic practice