Early onset or syndromic epilepsy

Gene: PRRT2

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)

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

• 23077018
• 24101679
• 22832103

Green List (high evidence)

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

• Wan et al (2011) Brain 134: 3493_3501
• Chen et al (2011) Nature Genet 43(12): 1252-1256
• Heron et al (2012) Am J Hum Genet 90: 152_160

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

Green List (high evidence)

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

• Wan et al (2011) Brain 134: 3493_3501
• Chen et al (2011) Nature Genet 43(12): 1252-1256
• Heron et al (2012) Am J Hum Genet 90: 152_160

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

Green List (high evidence)

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

• Wan et al (2011) Brain 134: 3493_3501
• Chen et al (2011) Nature Genet 43(12): 1252-1256
• Heron et al (2012) Am J Hum Genet 90: 152_160

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

Green List (high evidence)

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

• Wan et al (2011) Brain 134: 3493 3501
• Chen et al (2011) Nature Genet 43(12): 1252-1256
• Heron et al (2012) Am J Hum Genet 90: 152 160

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

Comment on list classification: Insufficient data for this phenotype

Created: 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.