Early onset or syndromic epilepsy

Gene: DBT

Green List (high evidence)

Gene is associated with Maple syrup urine disease, which can be associated with seizures if not properly controlled.

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
Maple syrup urine disease,type II 248600

Publications

• 1990841

I don't know

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: Alison Callaway and 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

Comment on list classification: Updated rating from Amber to Green following publication of two 2019 papers (PMID:31112740 and PMID:31119508) who report MSUD patients with seizures and biallelic variants in DBT. Each paper reports individuals from a different ethnic group. Sufficient unrelated cases for a diagnostic-green rating.

Created: 4 Jul 2019, 12:59 p.m. | Last Modified: 4 Jul 2019, 12:59 p.m.

Panel Version: 1.113

PMID:31112740. Yang et al 2019 identify a Chinese patient with MSUD (Patient 2) with compound het DBT variants: missense p.Leu69Arg and nonsense R291*. Patient 2 was recorded with Convulsions (Table 1). Leu69 is located in the LBD of the encoded BCKD protein, and therefore likely to affect the function of the protein. Segregation analysis was not performed. The 1000 Genome Project data was used to filter the data, and variants were validated by Sanger sequencing.

Created: 4 Jul 2019, 12:54 p.m. | Last Modified: 4 Jul 2019, 12:54 p.m.

Panel Version: 1.112

PMID:31119508. Abiri et al. 2019 investigated the mutation spectrum of MSUD patients in 40 unrelated Iranian families. 5 patients (P36-P40) had homozygous or compound het variants in DBT. 4/5 of these patients had seizures reported. Four of the DBT variants were novel. None of the variants are present in controls including ExAC and the Iranome. Different variants reported in each of the 5 patients suggesting the patients are unrelated.

Created: 4 Jul 2019, 12:39 p.m. | Last Modified: 4 Jul 2019, 12:39 p.m.

Panel Version: 1.110

Comment on list classification: Kept rating as Amber: DBT encodes the E2 subunit of the BCKD complex. The other complex subunits (BCKDHA and BCKDHB) are Green on this panel, and all 3 genes are associated with Maple syrup urine disease (MSUD, MIM:248600). Seizures are a recognised symptom of MSUD, and although there is generalized information about DBT causing intermediate forms of the disease with later-onset seizures, specific cases with DBT variants are required before promoting to Green.

Created: 3 Dec 2018, 11:55 a.m.

Green List (high evidence)

Seizures are a feature of this metabolic condition.

Created: 12 Aug 2018, 6:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Maple syrup urine disease, type II, MIM#248600

Variants in this GENE are reported as part of current diagnostic practice