Early onset or syndromic epilepsy
Gene: DPM1
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
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 seizuresCreated: 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.
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
Phenotypes for gene: DPM1 were changed from Congenital disorder of glycosylation, type Ie, 608799 to Congenital disorder of glycosylation, type Ie, OMIM:608799
Source Wessex and West Midlands GLH was added to DPM1.
Source NHS GMS was added to DPM1.
Zornitza Stark: Seizures are a feature of this
Gene: dpm1 has been classified as Green List (High Evidence).
Publications for gene: DPM1 were set to 23856421; 10642597; 10642602
Gene: dpm1 has been classified as Green List (High Evidence).
Publications for gene: DPM1 were set to
Mode of inheritance for gene: DPM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Expert Review Amber was added to DPM1. Panel: Genetic Epilepsy Syndromes
DPM1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
DPM1 was created by Sarah Leigh