Early onset or syndromic epilepsy
Gene: GAMT
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
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
Comment on phenotypes: added synonymsCreated: 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 associationCreated: 21 Nov 2018, 2:49 p.m.
Comment on publications: Added publications s to support upgrading of the gene to GreenCreated: 21 Nov 2018, 2:43 p.m.
Comment on mode of inheritance: Added MOI from external clinical review and publicationsCreated: 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 panelCreated: 21 Nov 2018, 2:22 p.m.
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
Source Wessex and West Midlands GLH was added to GAMT.
Source NHS GMS was added to GAMT.
Zornitza Stark: Seizures are part of the pheno
Gene: gamt has been classified as Green List (High Evidence).
Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase; GAMT deficiency
Publications for gene: GAMT were set to 15651030; 17101918; 15108290; 19027335
Gene: gamt has been classified as Green List (High Evidence).
Publications for gene: GAMT were set to
Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase
Mode of inheritance for gene: GAMT was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GAMT were changed from to Cerebral creatine deficiency syndrome 2, 612736; Seizures
Expert Review Amber was added to GAMT. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to GAMT. Panel: Genetic Epilepsy Syndromes
GAMT was added to Genetic Epilepsy Syndromes panel. Sources: Expert,Expert Review Red
GAMT was created by Sarah Leigh