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Genetic epilepsy syndromes

Gene: DHDDS

Green List (high evidence)

DHDDS (dehydrodolichyl diphosphate synthase subunit)
EnsemblGeneIds (GRCh38): ENSG00000117682
EnsemblGeneIds (GRCh37): ENSG00000117682
OMIM: 608172, Gene2Phenotype
DHDDS is in 12 panels

2 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AD dev delay and seizures with or without movement abnormalities (DEDSM), AR retinitis pigmentosa 59 sand AR ? Congenital disorder of glycosylation type1bb. DEDSM - early onset seizures with a myoclonic component. Hamdan et al, 2017 - 5 unrelated patients with global developmental delay and seizures in the 1st decade of life. 2 diff het de novo missense variants. No functional studies performed. In the glyocsylation phenotype - a patient reported by Sabry et al had seizures as part of his phenotype and died at 8 months - missense variant detected - yeast transfection studies done.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
?Congenital disorder of glycosylation, 613861 ; Developmental delay and seizures with or without movement abnormalities, 617836; Retinitis pigmentosa, 613861

Publications

Rebecca Foulger (Genomics England curator)

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 list classification: Added gene to panel and rated green based on literature evidence (PMID:29100083) and relevant OMIM phenotype (MIM:617836). 5 unrelated heterozygous cases in PMID:29100083 plus 1 compound het case in PMID:27343064 for a patient with a glycosylation disorder including seizures. Therefore sufficient (>3) unrelated seizure cases for a diagnostic rating.
Created: 11 Dec 2018, 11:53 a.m.
Comment on mode of inheritance: OMIM (and PMID:29100083) report AD inheritance for Developmental delay and seizures with or without movement abnormalities, 617836. In addition, Sabry et al (PMID:27343064) report one individual with a glycosylation disorder (MIM:613861) and epilepsy, carrying compound heterozygous variants in DHDDS. Therefore selected 'both monoallelic and biallelic' MOI.
Created: 11 Dec 2018, 11:50 a.m.
Sabry et al (PMID:27343064) report a patient with DHDDS deficiency and epilepsy amongst his phenotypes. The patient died at 8 months during a status epilepticus. The patient was compound heterozygous for variants in the DHDDS gene. The patient is also homozygous for the c.911 T>C (p.F304S) ALG6 variant that occurs in about one third of the population and does not cause CDG (but is a disease modifier to exacerbate symptoms in patients with glycosylation pathway defects).
Created: 11 Dec 2018, 11:48 a.m.
In 5 unrelated patients with developmental delay and seizures with or without movement abnormalities (DEDSM; 617836), Hamdan et al. (2017, PMID:29100083) identified 2 different de novo heterozygous missense mutations in the DHDDS gene (R37H and R211Q). These five individuals with de novo variants in DHDDS presented with a generalized epilepsy disorder with myoclonic seizures, either as myoclonic absences or as isolated cortical myoclonus, and sometimes with light sensitivity or fever susceptibility. Two of these individuals also presented with other generalized seizure types, including atonic seizures or generalized tonic-clonic seizures. In three individuals, EEG revealed clear generalized spike-wave discharges (and additional photosensitivity in one individual).
Sources: Literature
Created: 11 Dec 2018, 11:48 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Developmental delay and seizures with or without movement abnormalities, 617836; developmental and epileptic encephalopathy (DEE); ?Congenital disorder of glycosylation, type 1bb; 613861

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Literature
Phenotypes
  • Developmental delay and seizures with or without movement abnormalities, 617836
  • developmental and epileptic encephalopathy (DEE)
  • ?Congenital disorder of glycosylation, type 1bb,613861
OMIM
608172
Clinvar variants
Variants in DHDDS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to DHDDS.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to DHDDS.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Rebecca Foulger: In 5 unrelated patients with d

11 Dec 2018, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: DHDDS were changed from Developmental delay and seizures with or without movement abnormalities, 617836; developmental and epileptic encephalopathy (DEE); ?Congenital disorder of glycosylation, type 1bb; 613861 to Developmental delay and seizures with or without movement abnormalities, 617836; developmental and epileptic encephalopathy (DEE); ?Congenital disorder of glycosylation, type 1bb,613861

11 Dec 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dhdds has been classified as Green List (High Evidence).

11 Dec 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: dhdds has been classified as Green List (High Evidence).

11 Dec 2018, Gel status: 1

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: DHDDS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

11 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: DHDDS was added gene: DHDDS was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: DHDDS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DHDDS were set to 27343064; 29100083 Phenotypes for gene: DHDDS were set to Developmental delay and seizures with or without movement abnormalities, 617836; developmental and epileptic encephalopathy (DEE); ?Congenital disorder of glycosylation, type 1bb; 613861 Review for gene: DHDDS was set to GREEN