Early onset or syndromic epilepsy

Gene: DPM1

Green List (high evidence)

AR congenital disorder of glycosylation type Ie. Lim et al, 2000 - 2 patients with similar phenotypic and biochemical feautres suggestive of a disorder of glycosylation - both had seizures - 1 hom and the other compound het. Imbach et al,2000 - 2 sibs - severe dev delay, seizures and dysmorphic features - compound het variants. Garcia-Silva et al, 2004 - 9 year old girl with consang parents seizures part of phenotype - hom missense variant. Dancourt et al, 2006 - 2 sibs of consang Algerian parents- neither had severe epilepsy but older sib did have mild febrile seizures - hom splice site variant, parents het - patient cells had 8% residual enzyme activity and a more than 90% reduction in DPM1 transcript levels. Yang et al, 2013 - 2 months presented with nonfebrile seizures - compound het 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
Congenital disorder of glycosylation type Ie, 608799

Publications

• 23856421

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: 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 publications: Epilepsy is not reported in all patients. Severe epilepsy was not present in 2 French siblings with CDG1E, born of consanguineous Algerian parents, as reported Dancourt et al. (2006, PMID:16641202).

Created: 26 Nov 2018, 9:37 a.m.

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza. Confirmed DD-G2P gene for congenital disorder of glycosylation, which can present with seizures. Sufficient cases of seizures in patients with CDG1E (MIM:608799) for inclusion on panel: 4 unrelated cases in PMIDs 23856421, 10642597 and 10642602, several of which are compound heterozygous for a substitution AND a deletion in DPM1.

Created: 26 Nov 2018, 9:36 a.m.

Imbach et al. (2000, PMID:10642602) report a brother and sister with severe developmental delay, repeated seizures, and dysmorphic features. Both sibs were compound heterozygous for the 274C>G (R92G) transversion and a 628delC deletion in DPM1.

Created: 26 Nov 2018, 9:31 a.m.

Kim et al., 2000 (PMID:10642597) report a patient with CDG1E and a homozygous 274C-G transversion in the DPM1 gene (p.R92G). Another unrelated patient was compound heterozygous for the R92G variant and a 13-bp deletion in exon 4 that may result in an unstable transcript. Both patients were recorded with medically intractable seizures

Created: 26 Nov 2018, 9:30 a.m.

In a boy with congenital disorder of glycosylation type Ie (MIM:608799), Yang et al. (2013, PMID:23856421) identified compound heterozygous mutations in the DPM1 gene: a c.455G-T transversion (G152V) and an intragenic deletion from exons 3-7. The child had delayed psychomotor development and seizures as part of his clinical symptoms.

Created: 26 Nov 2018, 9:30 a.m.

Green List (high evidence)

Seizures are a feature of this metabolic disorder.

Created: 12 Aug 2018, 6:54 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ie, MIM#608799

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