Early onset or syndromic epilepsy

Gene: SLC1A4

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)

AR spastic tetraplegia, thin corpus callosum and progressive microcephaly - some patients may have seizures. Srour et al, 2015 - 2 sibs - consanguineous AJ parents - 1 had seizures. Heimer et al, 2015, 2 unrelated children. 1 of AJ descent and the other of Ashkenazi-Iraqi parents - both had epilepsy. Damseh et al, 2015 - 10 children from 8 families of AJ descent - 5 of which developed seizures. Common AJ variant E256K. In vitro studies show that the E256K variant reduces L-serine and L-alanine transport by 25% and 20% respectively. Another variant R457W - same functional work showed no measurable substrate transport activity. Pironti et al, 2018 - novel hom variant identifed in an Italian boy - had epilepsy. Conroy et al, 2016 - hom nonsense variant detected in an Irish proband who had seizures.

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
Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, 616657

Publications

• 26138499
• 26041762

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. Single variant originally only recorded in cases with Ashkenazi Jewish heritage, this variant and at least two others have now been reported in additional unrelated cases from other populations.

Created: 26 Sep 2018, 10:13 a.m.

Green List (high evidence)

Multiple affected individuals reported in the literature, seizures/EE are part of the phenotype. While initial reports identified a recurrent missense variant in individuals of Ashkenazi Jewish ancestry, there have been more recent reports of individuals from other ethnic backgrounds with different variants. Gene is also relevant to the ID panel.

Created: 4 Sep 2018, 3:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657

Publications

• 29989513
• 27193218
• 26138499
• 26041762
• 25930971

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