Early onset or syndromic epilepsy

Gene: BSCL2

I don't know

Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should change from 'BOTH monoallelic and biallelic' to 'BIALLELIC': just one monoallelic case so far, which could be a false positive.

Created: 25 Nov 2019, 9:20 p.m. | Last Modified: 25 Nov 2019, 9:20 p.m.

Panel Version: 1.469

Comment on mode of inheritance: PMID:31369919 (Fernandez-Marmiesse et al., 2019) report 2 siblings with profound refractory epilepsy and neurological regression. A de novo Met189Lys variant in BSCL2 was detected that was absent in the parents and unaffected sibling. This is the first evidence of an association between a heterozygous BSCL2 variant and EIEE, and supports an AD+AR Mode of inheritance.

Created: 24 Oct 2019, 1:21 p.m. | Last Modified: 24 Oct 2019, 1:21 p.m.

Panel Version: 1.386

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

Green List (high evidence)

Encephalopathy, progressive, with or without lipodystrophy - AR. AR progressive encephalopathy with or without lipodystrophy - severe neurodegenerative disirder - develpmental regression of motor and cognitive skills in forst year of life often leading to death in first decade. Gullen-Navarro et al, 2013 - 6 children from 4 families from Murcia with severe prog encephalopathy - feaures incl seizures, 5/6 died between the ages of 6 and 8. Hom or compound het truncating variants identified in all, all patients had c.985C>T on at least 1 allele. Opri et al, 2016 - 3 patients with progressive myoclonic epilepsy -2 hom for a fs variant and 1 compund het for 2 fs mutations.

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
Lipodystrophy, congenital generalized, type 2,269700; Neuropathy, distal hereditary motor, type VA,600794; Silver spastic paraplegia syndrome,270685; Encephalopathy, progressive, with or without lipodystrophy,615924

Publications

• 23564749

Green List (high evidence)

Three biallelic variants were reported in encephalopathy, progressive, with or without lipodystrophy 615924 which includes seizures, cognitive decline and death in childhood. The variants were found in one homozygous case and two unrelated compound heterozygotes (one inferred from parental genotypes). Variant c.985C>T p.E329* was identified as a potiential founder variant (PMID 23564749).

Created: 14 Dec 2017, 4:45 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, with or without lipodystrophy 615924; Lipodystrophy, congenital generalized, type 2 269700; Neuropathy, distal hereditary motor, type VA 600794; Silver spastic paraplegia syndrome 270685

Publications

• 24896178
• 26503795
• 23564749
• 15181077