Early onset or syndromic epilepsy
Gene: SCN1B
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
AR EIEE52, AD generalised epilepsy with febrile seizures and also assoc with atrial fibrillation, cardiac conduction defect and Brugada syndrome. AD epilepsy - Wallace et al 1998 and 2002 - 2 Australian families with this variant. First family large 6 generation family where 42 individuals had a history of seizures. Did see unaffected carriers suggests reduced penetrance . AR epilepsy - Patino et al, 2009 - boy born of consang Moroccan parents - hom missense variant, in vitro functional studies showed that the mutant protein was poorly expressed at the cell surface, despite robist intracellular expression, consistent with a tracking defect to the membrane. Carrier parents did not have seizures. Ogiwara et al, 2012 - Japanese man with unrelated parents hom for a missense variant. Functional work not done. 17 different variants reported on HGMD Pro in association with epilepsy/seizures and number of cases on OMIM.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Atrial fibrillation, familial,615377; Brugada syndrome,612838; Cardiac conduction defect, nonspecific,612838; Epilepsy, generalized, with febrile seizures plus, type 1,604233; Epileptic encephalopathy, early infantile, 52,617350
Publications
Comment on mode of inheritance: Epilepsy, generalized, with febrile seizures plus, type 1 604233 monoallelic not imprinted;
Epileptic encephalopathy, early infantile, 52 617350 biallelicCreated: 4 Apr 2018, 3:02 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Evidence of pathogenicity exists for M_001037.4(SCN1B):c.363C>G (p.Cys121Trp); few if any other variants have sufficient evidence for pathogenicity currentlyCreated: 8 May 2016, 7:11 p.m.
Comment when marking as ready: Confirmed DD gene and all 4 reviewers agree this should be green. Mode of inheritance and loss-of-function mechanism confirmed.Created: 21 Jan 2016, 11:52 a.m.
Comment on mode of inheritance: Confirmed and not on imprinted gene list.Created: 21 Jan 2016, 11:51 a.m.
Phenotypes for gene: SCN1B were changed from Epilepsy, generalized, with febrile seizures plus, type 1 604233 AD; Epileptic encephalopathy, early infantile, 52 617350 AR to Developmental and epileptic encephalopathy 52, OMIM:617350 (AR); Generalized epilepsy with febrile seizures plus, type 1, OMIM:604233 (AD)
Publications for gene: SCN1B were set to 12011299; 16205844; 9697698
Source Wessex and West Midlands GLH was added to SCN1B.
Source NHS GMS was added to SCN1B.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to SCN1B. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to SCN1B. Panel: Genetic Epilepsy Syndromes
Mode of inheritance for SCN1B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for SCN1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for SCN1B were set to Epilepsy, generalized, with febrile seizures plus, type 1 604233 AD; Epileptic encephalopathy, early infantile, 52 617350 AR
Publications for SCN1B were set to 12011299; 16205844; 9697698
SCN1B was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert
SCN1B was created by Sarah Leigh