Early onset or syndromic epilepsy

Gene: GAMT

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 Cerebral creatine deficiency syndrome 2 (CCDS2) - features include intractable seizures. Stockler et al, 1994 & 1996 - 2 patients - 1 def had intractable seizures, 1 patient hom and 1 compund het. Caldeira Arajuo et al, 2005 - 4 patients with GMAT defic. (3 related sibs and cousin) 3/4 had convulsions - 3 family members and an isolated patient, hom GAMT variants identified. Lion-Francois et al, 2006 - N African patient had seizures - hom missense variant. Mercimek-Mahmutoglu et al, 2014 - In 74 patients - 5o duff mutations identified with missense being the most common. Here reporting 13 new patients with 6 novel mutatons and functional analysis of 19 missense variants (seizures/epilepsy seen in 15/21).

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
Cerebral creatine deficiency syndrome, 612736

Publications

• 19027335

Comment on phenotypes: added synonyms

Created: 21 Nov 2018, 2:52 p.m.

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association

Created: 21 Nov 2018, 2:49 p.m.

Comment on publications: Added publications s to support upgrading of the gene to Green

Created: 21 Nov 2018, 2:43 p.m.

Comment on mode of inheritance: Added MOI from external clinical review and publications

Created: 21 Nov 2018, 2:24 p.m.

Comment on phenotypes: I did not add the expert review phenotype Krabbe disease as the review was related to the previously reviewed gene GALC. Cerebral creatine deficiency syndrome 2, 612736 is the disorder associated to variants of this gene, and is relevant for inclusion on the Genetic Epilepsy Syndromes panel

Created: 21 Nov 2018, 2:22 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 14 Aug 2018, 12:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Krabbe disease, MIM#245200

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)