Congenital disorders of glycosylation

Gene: UGGT1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (10 unrelated families and functional evidence) for the promotion of this gene to green rating in this panel on the next GMS update.

Created: 30 Sep 2025, 9:31 a.m. | Last Modified: 30 Sep 2025, 9:31 a.m.

Panel Version: 7.8

PMID:40267907 (2025) reported biallelic UGGT1 variants (either homozygous or compound heterozygous) in fifteen individuals from ten unrelated families of various descents as a cause of congenital disorder of glycosylation. There are a total of nine different UGGT1 variants identified from these patients including one nonsense variant, four insertion or deletion (indel) variants and four missense variants. All variants are ultra-rare or absent from gnomAD v.4.1.0.

The cardinal clinical features of UGGT1-CDG involve developmental delay, intellectual disability (severe ID reported in all tested individuals - ten from six unrelated families), seizures, characteristic facial features, and microcephaly in the majority (9/11 affected individuals for whom measurements were available).

Molecular studies showed that pathogenic UGGT1 variants impair UGGT1 glucosylation and catalytic activity, disrupt mRNA splicing, or inhibit endoplasmic reticulum (ER) retention.

This gene has been associated with UGGT1-related congenital disorder of glycosylation with neurodevelopmental impairment phenotype on the DD panel of Gene2Phenotype with 'moderate' rating, but not yet with any phenotypes in OMIM.

Created: 30 Sep 2025, 9:26 a.m. | Last Modified: 30 Sep 2025, 9:26 a.m.

Panel Version: 7.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
congenital disorder of glycosylation, MONDO:0015286

Publications

• 40267907

Green List (high evidence)

Dardas et al report biallelic UGGT1 variants in 10 families (15 individuals), with more severe phenotypes seen with biallelic loss of function variants. UGGT1 variants were shown to impair UGGT1 glycosylation and catalytic activity.
Sources: Literature

Created: 16 Sep 2025, 10:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability; seizures; characteristic facial features; microcephaly; congenital heart malformations, variable skeletal abnormalities; hepatic and renal involvement; polycystic kidneys

Publications

• PMID: 40267907

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