Early onset or syndromic epilepsy

Gene: EML1

Green List (high evidence)

AR Band heterotopia. Keilar et al, 2014 - French family with 3 brothers with severe dev delay, ID 2/3 refractory epilepsy. Also reported an unrelated boy born to consng Moroccan parents with macrocehaly, congenital hydrocephalus, severe psychomotor delay and seizures.Hom/compound het variants identified - mutations co seg with disese in both families. Shaheen et al, 2017 - consang Saudi family - 4 individuals had hydrocephalus, 2 aff individuals deceased. Only have clinical info for proband who had intractable epilepsy.hom nonsense variant identified in proband also in 1 of the other aff relatives (no DNA on deceased). Mouse mutant model has seizures and sutle learning difficulties assoc with heterotopic nerons in the braIn white matter.

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
Band heterotopia,600348

Publications

• 24859200

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: Added EML1 as a green gene to the panel after advice from Arianna Tucci. All 3 published unrelated families (PMIDs:24859200 and 28556411) with EML1 variants display epilepsy/seizures.

Created: 24 Oct 2017, 3:31 p.m.

PMID:28556411 (Shaheen et al., 2017) identify a 3rd case: a homozygous truncating variant (NM_004434.2:c.1567C>T, p. [Arg523*]) in EML1 in a 2-year-old girl with congenital hydrocephalus, profound global developmental delay and intractable epilepsy.

Created: 24 Oct 2017, 3:28 p.m.

Upon screening of patients with cortical malformations, Kielar et al (PMID:24859200, 2014) report 3 French brothers with a compound het variant (c.481C>T, p.Arg138*, and c.796A>G, p.T243A) in EML1. Two of the brothers had epilepsy. An unrelated Moroccan boy with congenital hydrocephalus, severe psychomotor delay and seizures was homozygous for a W225R variant.

Created: 24 Oct 2017, 3:28 p.m.

Added to EE panel on advice from Arianna Tucci and 3 published cases.

Created: 24 Oct 2017, 3:28 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Band heterotopia, 600348

Publications

• 24859200
• 28556411