Early onset or syndromic epilepsy
Gene: LARGE1
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: Alison Callaway and John Taylor. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Congenital Muscular Dystrophy would be a better panel for this gene.LARGE1 appears to be associated predominantly with congenital muscular dystrophy, although there is some association with Walker-Warburg syndrome which may sometimes be associated with seizures, secondary to the brain abnormalities (e.g. cobblestone lissencephaly which can lead to hydrocephalus)Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation) type B, 608840
Comment when marking as ready: Seizures are more common features of other dystroglycanopathies, therefore LARGE1 will remain an amber gene as there is not enough evidence to promote it to a green gene currently. I have added the 'watchlist' tag.Created: 3 Dec 2018, 10:40 a.m.
Comment on list classification: Muscular dystrophy-dystroglycanopathy was confirmed by both OMIM and Gene2Phenotype; however, seizures/epilepsy was not listed as a phenotype for either databases. There is only one reported case of a patient with mutations in LARGE1 who also have seizures (PMID: 24709677). Therefore not enough evidence to promote to green status.Created: 21 Nov 2018, 10:45 a.m.
Seizures are part of the phenotype of dystroglycanopathies.Created: 16 Aug 2018, 11:25 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM#613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM#608840
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to LARGE1.
Source NHS GMS was added to LARGE1.
Zornitza Stark: Seizures are part of the pheno
Gene: large1 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: LARGE1.
Gene: large1 has been classified as Amber List (Moderate Evidence).
Gene: large1 has been classified as Amber List (Moderate Evidence).
Publications for gene: LARGE1 were set to
Mode of inheritance for gene: LARGE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, 608840
Expert Review Amber was added to LARGE1. Panel: Genetic Epilepsy Syndromes
LARGE1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
LARGE1 was created by Sarah Leigh