Early onset or syndromic epilepsy
Gene: RELN
AR Lissencephaly 2 and AD familial temporal lobe epilepsy 7 (ETL7). AR Lissencephaly - Hong et al 2000 - 2 consang families (British and Saudi Arabian) - aff family members were found to have had hom RELN variants. Zaki et al 2007 - consang Egyptian marriage - hom apparantly balanced reciprocal translocation in 2 aff sibs - disrupts the RELN gene. All affecteds had seizures. ETL7 - charecterised by focal seizures. Dazzo et al, 2015 - 7 unrelated families of Italian descent - 7 diff het variants. Functional studies not performed but 3D modelling predicts mutations would result in structural defects and protein misfolding which could lead to degredation of the altered proteins. Aff individuals from 4 families had reduced up to 50%) serum levels of the main 310-kD reelin isform compared to controls - poss due to impaired secretion of the altered proteins from hepatocytes. On HGMD Pro - other associations include Hypogonadotrophic hypogonadism and Autism spectrum disorder. Obvioulsy assoc with seizures, but not the case for all variants.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
Lissencephaly 2 (Norman-Roberts type), 257320; {Epilepsy, familial temporal lobe, 7}, 616436
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 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
Comment on mode of inheritance: Updated MOI from monoallelic to 'BOTH monoallelic and biallelic' based on papers reporting seizures as part of AR lissencephaly phenotype: PMID:17431900 (Zaki et al 2007) and PMID:10973257 (Hong et al, 2000).Created: 11 Jul 2019, 8:58 a.m. | Last Modified: 11 Jul 2019, 8:58 a.m.
Panel Version: 1.153
Associated with {Epilepsy, familial temporal lobe, 7} 616436 in OMIM and not in Gen2Phen. At least 4 missense variants identified in unrelated families.Created: 23 Jul 2018, 1:56 p.m.
Comment on phenotypes: Biallelic variants are associated with Lissencephaly 2 (Norman-Roberts type) 257320Created: 23 Jul 2018, 1:49 p.m.
Comment on mode of inheritance: Biallelic variants are associated with Lissencephaly 2 (Norman-Roberts type) 257320.Created: 23 Jul 2018, 1:47 p.m.
Phenotypes for gene: RELN were changed from {Epilepsy, familial temporal lobe, 7} 616436 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; {Epilepsy, familial temporal lobe, 7}, OMIM:616436
Publications for gene: RELN were set to 26046367
Source Wessex and West Midlands GLH was added to RELN.
Source NHS GMS was added to RELN.
Mode of inheritance for gene: RELN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sarah Leigh: Comment on mode of inheritance
Gene: reln has been classified as Green List (High Evidence).
Source Victorian Clinical Genetics Services was removed from RELN. Panel: Genetic Epilepsy Syndromes Literature was added to RELN. Panel: Genetic Epilepsy Syndromes Phenotypes for gene RELN were set to {Epilepsy, familial temporal lobe, 7} 616436 Penetrance for gene RELN was set to Incomplete
Phenotypes for gene: RELN were set to {Epilepsy, familial temporal lobe, 7} 616436
Mode of inheritance for gene: RELN was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELN were set to 26046367
Expert Review Amber was added to RELN. Panel: Genetic Epilepsy Syndromes
RELN was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
RELN was created by Sarah Leigh