Intellectual disability
Gene: DHDDS

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

2 reviews

Arina Puzriakova (Genomics England Curator)

The mode of inheritance of this gene has been updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.

Panel Version: 4.53

Comment on mode of inheritance: MOI should be updated from 'Both mono- and biallelic' to 'Monoallelic' at the next GMS panel update. Monoallelic variants are associated with a neurodevelopmental disorder comprising DD/ID, epilepsy and a variable movement disorder phenotype - >3 unrelated individuals reported in literature. To date, only one individual with biallelic variants and ID has been reported (PMID: 27343064). This patient presented with glycosylation defects but no corroborating cases have been reported since.
As only one patient has been described with biallelic inheritance and this phenotype, MOI should be set to 'Monoallelic' until evidence of additional cases emerges - biallelic variants would still be picked up by the Genomics England pipeline under this MOI.
Created: 28 Oct 2021, 1:34 p.m. | Last Modified: 28 Oct 2021, 1:34 p.m.

Panel Version: 3.1395

Created: 28 Oct 2021, 1:34 p.m.
Last Modified: 28 Oct 2021, 1:34 p.m.
Panel version: 4.53

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Comment on list classification: Added DHDDS to panel and rated Green: Probable DD-G2P gene for 'Epilepsy and intellectual disability' and sufficient unrelated (>3) cases of ID phenotype associated with heterozygous DHDDS variants from PMID:29100083. Plus compound het case of patient with glycosylation disorder and complex developmental phenotypes from PMID:27343064.
Created: 11 Dec 2018, 2:46 p.m.

Comment on mode of inheritance: Sabry et al (PMID:27343064) report a patient with DHDDS deficiency. 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). During his short life, the boy made little psychomotor acquisitions, had no eye contact, poor sucking with frequent regurgitations and failure to thrive. I have selected both monoallelic and biallelic MOI to cover MIM:617836 (AD) and future cases where ID presents as a symptom of a recessive glycosylation disorder.
Created: 11 Dec 2018, 12:20 p.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). The ID phenotype of patients covers severe/moderate-to-severe ID and global developmental delay.
Sources: Literature
Created: 11 Dec 2018, 12:06 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Developmental delay and seizures with or without movement abnormalities, 617836

Publications

Created: 11 Dec 2018, 12:06 p.m.

Panel version: 2.580

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

NHS GMS
Expert Review Green
Literature

Phenotypes

Developmental delay and seizures with or without movement abnormalities, OMIM:617836

OMIM

608172

Clinvar variants

Variants in DHDDS

Penetrance

None

Publications

Panels with this gene