Congenital disorders of glycosylation

Gene: DDOST

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:41 p.m. | Last Modified: 24 Feb 2025, 5:41 p.m.

Panel Version: 6.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (two unrelated patients and some functional evidence) for the promotion of this gene to green rating in the next GMS update.

Created: 17 Jul 2024, 2:01 p.m. | Last Modified: 17 Jul 2024, 2:01 p.m.

Panel Version: 5.6

PMID:22305527 reported the identification of compound heterozygous variants in DDOST gene (c.1265_1286del22/ p.Ile422Thrfs∗7 & c.650G>A/ p.Gly217Asp) in an untyped congenital disorder of glycosylation (CDG) patient. Biochemical analysis revealed that N-glycosylation was decreased in the patient's fibroblasts and complementation with wild-type-DDOST cDNA in patient fibroblasts restored glycosylation, indicating that the mutations were pathological.

PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient.

This gene has been associated with relevant phenotypes in both OMIM (MIM #614507) and Gene2Phenotype (with 'definitive' rating on the DD panel).

Created: 17 Jul 2024, 1:58 p.m. | Last Modified: 17 Jul 2024, 1:58 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ir, OMIM:614507

Publications

• 22305527
• 34462534

Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least 2 variants reported as compound heterozygotes in one patient.

Created: 15 Dec 2016, 4:13 p.m.

Red List (low evidence)

A single patient has been reported. The biochemical function of this protein suggests that this gene should be included in the list, but there are no more confirmed patients thus far.

Created: 12 Dec 2016, 1:40 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 22305527