Early onset or syndromic epilepsy

Gene: ADRA2B

Red List (low evidence)

This gene-disease association has been REFUTED by Corbett et al 2019, who identified an alternative cause in the original families.

Created: 7 Jan 2020, 4 a.m. | Last Modified: 7 Jan 2020, 4 a.m.

Panel Version: 2.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cortical myoclonus and epilepsy

Publications

• 24114805
• 21937992

I don't know

Added 'for-review' tag to alert GLH to downgraded rating.

Created: 18 May 2020, 2:46 p.m. | Last Modified: 18 May 2020, 2:46 p.m.

Panel Version: 2.53

Comment on list classification: Downgraded rating from Amber to Red following PMID:31664034 (2019) publication that finds an alternative cause for epilepsy in the earlier reported patients, suggesting the the ADRA2B allele is not causative. MIM:607876 is now associated with a repeat expansion in STARD7, and not ADRA2B.

Created: 18 May 2020, 2:44 p.m. | Last Modified: 18 May 2020, 2:44 p.m.

Panel Version: 2.53

PMID:18231815: Direct sequencing of the ADRA2B gene in pedigrees from southern Italy that were described as having familial adult myoclonic epilepsy by Madia et al. (2008) did not reveal any pathogenic mutations.

Created: 18 May 2020, 2:37 p.m. | Last Modified: 18 May 2020, 2:37 p.m.

Panel Version: 2.51

PMID:31664034. Corbett et al., 2019. In 158 affected individuals from 22 unrelated families with MIM:607876, Corbett et al. (2019) identified a heterozygous 5-bp repeat expansion, (ATTTC)n, in the STARD7 gene. The cohort included 2 families who had previously been identified as having an ins/del mutation in the ADRA2B gene (Guerrini et al., 2001 PMID:11701600, and De Fusco et al., 2014, PMID:24114805), suggesting the the ADRA2B allele is not causative.

Created: 18 May 2020, 2:37 p.m. | Last Modified: 18 May 2020, 2:37 p.m.

Panel Version: 2.51

Comment on phenotypes: OMIM disorder 'Epilepsy, familial adult myoclonic, 2, 607876' is now associated with the STARD7 gene. Therefore removed MIM:607876 from the phenotype field of ADRA2B.

Created: 18 May 2020, 2:23 p.m. | Last Modified: 18 May 2020, 2:23 p.m.

Panel Version: 2.51

This gene was part of an initial gene list 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: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

AD familial adult myoconic epilepsy 2 (FAME2) - generalised tonic clonic seizures are a feauture but they are infrequent. Guerrini et al, 2001 - Large Italian kindred -11 aff individuals all had infrequent generalidsed tonic-clonic seizures and 3 also had intractable complex partial seizures. Labuge et al 2002 - 4 generation European family - 8/13 generalised tonic-clonic seizures. De Falco et al, 2003 - 2 Italian families - most patients had infrequent seizures - no variant identified - Madia et al, 2008. De Fusco et al, 2014 - 4 generation Italian family - 5 aff - 4 had generalised tonic clonic seizures and 2 had drug-resistant focal seizures also looked at Guerrini et al 2000 family - all had het delins mutation - haplotype analysis suggested a founder effect, functional studies suggest GOF.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, myoclonic, familial adult, 2, 607876

Publications

• 11701600