Early onset or syndromic epilepsy

Gene: PURA

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 mental retardation 31 (MRD31). Lalani et al, 2014 - 11 unrelated children with a similar neurodevelopmental disorder - amlonst all had early-onset seizures, often myoclonic but also generalised - all had de novo het mutations in the PURA gene (4 trunating, 5 missense and 2 in-frame del - no functional work). Hunt et al, 2014 - 4 unrelated girls with neurodevelopmental delay - 3/4 had seizures - found 4 de novo het mutations (2 truncating, 1 missense, 1 in frame del) - no functional work. Tanaka et al, 2015 - 6 unrelated children, 2/6 had seizure-like activity - 6 diff de novo het mutations (missense, frameshift and small intragenic dels) - no functional work. DDD study 2015 - 3 female patients with dev delay all had het de novo PURA mutations - no mention of seizures. Lee et al, 2017 - report 18 new individuals with de novo pathogenic PURA variants - 9/18 had epilepsy.

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
Mental retardation, 616158

Publications

• 25439098

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• Hunt et al (2014) Lalani (2014)

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

Publications

• Hunt et al (2014) Lalani (2014)

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

Publications

• Hunt et al (2014) Lalani (2014)

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

Publications

• Hunt et al (2014) Lalani (2014)

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

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, 11:46 a.m.

Comment on mode of inheritance: Confirmed with G2P and OMIM, and not on the imprinted gene list.

Created: 21 Jan 2016, 11:44 a.m.

Comment on phenotypes: Sourced from G2P and OMIM.

Created: 21 Jan 2016, 11:43 a.m.

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).

Created: 12 Nov 2015, 4:20 p.m.