Early onset or syndromic epilepsy
Gene: MLC1
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Megalencephalic leukoencephalopathy with subcortical cysts, 604004
Publications
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. 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
In a woman with megalencephalic leukoencephalopathy with subcortical cysts-1 (MLC1; 604004), Lopez-Hernandez et al. (2011, PMID:21624973) identified a homozygous misssense 206C-T variant in the MLC1 gene (p.S69L). The patient had epilepsy amongst her symptoms.Created: 3 Dec 2018, 9:22 a.m.
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza. Plus the onset of epileptic seizures is an integral part of the MLC phenotype (PMID:29466841) with plenty of seizure cases in MLC1 patients in PMIDs:29466841 and 21624973.Created: 3 Dec 2018, 9:21 a.m.
PMID:29466841 (Dubey et al, 2018) analyzed an MLC patient inventory to study occurrence of seizures in MLC. 141 patients had recessive MLC1 variants, and 17 had recessive GLIALCAM (HEPACAM) variants. 75.8% of patients with MLC1 variants had at least one seizure before age 25. Of all patients with seizures (includes MLC1 and HEPACAM patients), 73% had epilepsy that was well controlled with medication. PMID:29466841 also show a mouse model with spontaneous epileptiform brain activity and a lowered threshold for induced seizures in MLC mice (MLC mice includes both Mlc1-/- and Hepacam-/-).Created: 3 Dec 2018, 9:19 a.m.
Seizures are part of the phenotype of this leukodystorphy.Created: 16 Aug 2018, 12:04 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Megalencephalic leukoencephalopathy with subcortical cysts, MIM#604004
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to MLC1.
Source NHS GMS was added to MLC1.
Zornitza Stark: Seizures are part of the pheno
Gene: mlc1 has been classified as Green List (High Evidence).
Gene: mlc1 has been classified as Green List (High Evidence).
Publications for gene: MLC1 were set to 21624973; 2946684
Publications for gene: MLC1 were set to
Phenotypes for gene: MLC1 were changed from Megalencephalic leukoencephalopathy with subcortical cysts, 604004 to Megalencephalic leukoencephalopathy with subcortical cysts, 604004; generalized tonic-clonic seizures; focal seizures
Mode of inheritance for gene: MLC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts, 604004
Expert Review Amber was added to MLC1. Panel: Genetic Epilepsy Syndromes
MLC1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
MLC1 was created by Sarah Leigh