Early onset or syndromic epilepsy
Gene: PAFAH1B1
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
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
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.
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
Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1 607432 to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Source Wessex and West Midlands GLH was added to PAFAH1B1.
Source NHS GMS was added to PAFAH1B1.
Zornitza Stark: Seizures are part of the pheno
Gene: pafah1b1 has been classified as Green List (High Evidence).
Phenotypes for gene: PAFAH1B1 were changed from to Lissencephaly 1 607432
Publications for gene: PAFAH1B1 were set to
Mode of inheritance for gene: PAFAH1B1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: pafah1b1 has been classified as Green List (High Evidence).
Expert Review Amber was added to PAFAH1B1. Panel: Genetic Epilepsy Syndromes
PAFAH1B1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PAFAH1B1 was created by Sarah Leigh