Early onset or syndromic epilepsy

Gene: YWHAG

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

Green List (high evidence)

AD Early infantile epileptic encephalopathy - early onset seizures in most patients followed by intellectual disability, variable behavioural abnormalities and sometimes additional neurological features. Only 5 reported cases on HGMD - all missense 3/5 = epilepsy.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy early infantile 56, 605356

Publications

• 28777935

Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene.
Guella et al. (2017) PMID: 28777935 reported 4 unrelated patients with early infantile epileptic encephalopathy-56 (EIEE56; 617665) and identified de novo heterozygous missense mutations in the YWHAG gene. The authors also noted that 2 other patients with de novo heterozygous mutations in the YWHAG gene (c.148A>C, p.K50Q; c.398A>C, p.Y133S) had been reported by De Rubeis et al. (2014) PMID:25363760 and the Deciphering Developmental Disorders Study (2017) PMID:28135719, but no clinical details had been provided. There is also a mouse model to support this correlation : Guella et al. (2017) noted that a decrease or increase in Ywhag in mice leads to delayed neuronal migration of pyramidal neurons in the developing brain (PMID: 26297819, 27288018) and that atypical neuronal migration has been implicated in epilepsy.

Created: 4 Sep 2018, 10:39 a.m.

Comment on phenotypes: Epileptic encephalopathy, early infantile, 56 617665

Created: 4 Sep 2018, 10:34 a.m.

Green List (high evidence)

Four unrelated individuals reported with de novo variants in this gene and EE.

Created: 22 Aug 2018, 9:07 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 56, MIM#617665

Publications

• 28777935

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