Early onset or syndromic epilepsy
Gene: YWHAG
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
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
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 617665Created: 4 Sep 2018, 10:34 a.m.
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
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to YWHAG.
Source NHS GMS was added to YWHAG.
Zornitza Stark: Four unrelated individuals rep
Gene: ywhag has been classified as Green List (High Evidence).
Gene: ywhag has been classified as Green List (High Evidence).
Mode of inheritance for gene: YWHAG was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YWHAG were set to 26297819; 27288018; 28777935; 25363760
Phenotypes for gene: YWHAG were set to Epileptic encephalopathy, early infantile, 56 617665
Expert Review Amber was added to YWHAG. Panel: Genetic Epilepsy Syndromes
YWHAG was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
YWHAG was created by Sarah Leigh