Early onset or syndromic epilepsy
Gene: PRRT2
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
AD benign familial infantile seizures 2 (BFIS2), AD episodic kinesigenic dyskinesia 1 (EKD1), AD familial infantile convulsions with paroxysmal choreoathetosis (ICCA).Wang et al, 2011 - 2 large Han Chinese families - 2 diff het truncating variants - completely segregated with phenotype (EKD1) and 2 patients in each family had ICCA. Heron et al, 2012 - 5/6 families with ICCA identified 1 of 3 diff het mutations. Het PRRT2 mutations were also found in 14/17 families with BFIS2), common mutation seen - 649insC. Lee et al, 2012 - het mutations in this gene in affected families with ICCA - identified mutations in 24/25 additional families, again 649insC most common. Ono et al, 2012 - idenitifed 649dupC in 14/15 Japanese famiies with EKD1 some of whichg also had ICCA, and 2 families with BFIS2. In one family - arisen de novo.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis,602066; Episodic kinesigenic dyskinesia,128200; Seizures, benign familial infantile,605751
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis; Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis; Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis; Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis; Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Insufficient data for this phenotypeCreated: 8 May 2016, 7 p.m.
Comment when marking as ready: Confirmed DD gene and all 4 reviewers agree this should be green. Mode of inheritance and loss-of-function mechanism confirmed.Created: 21 Jan 2016, 11:41 a.m.
Comment on mode of inheritance: Confirmed with G2P and OMIM, and not on imprinted gene list.Created: 21 Jan 2016, 11:40 a.m.
Source Wessex and West Midlands GLH was added to PRRT2.
Source NHS GMS was added to PRRT2.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to PRRT2. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to PRRT2. Panel: Genetic Epilepsy Syndromes
PRRT2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert,UKGTN,Expert Review Green
PRRT2 was created by Sarah Leigh