Early onset or syndromic epilepsy

Gene: AMT

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 Glycine encephalopathy - neonatal and infantile forms associated with seizures but not the mild or late-onset forms. With neonatal form may not survive to point of developing seizures. (This gene encodes the T protein). Swanson et al, 2015 - reviewed 124 patients with severe nonketotic hyperglycinemia (disorder characterised by intellectual disability, seizures and spasticity) - found 18 novel mutations in AMT - RNA splicing used to show retention of intronic sequence for 1 intronic variant, expression atudies done on some missense variants - support pathogenicity. Coughlin et al, 2017 - reveiwng families with classic nonketotic hyperglycinemia - 578 families - 410 unique mutations - 80% in GLDC. missense mutations most often recurring (R320H seen in 16% of cases)- most common type of disease-causing mutation in AMT.

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
Glycine encephalopathy, 605899

Publications

• 25231368

Comment on phenotypes: Glycine encephalopathy 605899

Created: 17 Jul 2018, 9:42 a.m.

Comment on list classification: Based on review by Dr Arianna Tucci (Genomics England Clinical Fellow and Curator)

Created: 17 Jul 2018, 9:40 a.m.

Green List (high evidence)

Associated with Glycine encephalopathy in OMIM, and epilepsy is part of the phenotype

Created: 5 Jul 2018, 2:06 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycine encephalopathy 605899