Early onset or syndromic epilepsy

Gene: PAFAH1B1

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)

Associated with AD lissencephaly 1 and subcortical laminar heterotopia. Is associated with epilepsy - Saillour et al, 2009 = 40/63 patients with posterior predominant lissencephaly had a LIS1 mutation or deletion - 82.9% had early onset seizures and 48.7% had seizures more often than daily. Cardoso et al, 2002 65/98 patients with isolated lissencephaly or MLDS had large deletions of the LIS1 gene. Among 41 intragenic LIS1 mutations, 36(88%)resulted in a truncated or internally deleted protein, 5/41 missense. Saillour et al, 2009 - 40/63 patients with gene defects - 8 small dels and 31 het LIS1 mutations including 12 nonsense, 8 fs, 6 missense and 5 splicing. All confirmed 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
Lissencephaly, 607432; Subcortical laminar heterotopia, 607432

Publications

• 11502906
• 11754098

Comment when marking as ready: Sufficient cases with PAFAH1B1 variants in Lissencephaly 1 and reports of seizures.

Created: 14 Nov 2018, 5:03 p.m.

Comment on list classification: Numerous cases of variants in the PAFAH1B1 gene in patients with Lissencephaly 1 and reporting seizures.

Created: 14 Nov 2018, 4:59 p.m.

PAFAH1B1 is associated with Lissencephaly 1 in OMIM and Gene2Phenotype (confirmed).

Numerous SNVs and large deletions in patients with Lissencephaly have been reported. Many cases with seizures reported (see PMID: 19667223 for example).

Created: 14 Nov 2018, 4:58 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this brain development disorder.

Created: 18 Aug 2018, 8:53 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Lissencephaly 1, MIM#607432

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