Congenital disorders of glycosylation

Gene: STT3A

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:14 a.m. | Last Modified: 1 Feb 2023, 9:14 a.m.

Panel Version: 3.4

Comment on mode of inheritance: Should be updated from biallelic to both mono- and biallelic at the next GMS panel update as per review by Zornitza Stark. Both MOIs are also now recognised in OMIM.

Created: 18 Jul 2022, 2:44 p.m. | Last Modified: 18 Jul 2022, 2:44 p.m.

Panel Version: 2.91

Comment on list classification: There is enough evidence to support a gene-disease association, and so STT3A should be promoted from Amber to Green at the next GMS panel update (added 'for-review' tag).

At least 7 individuals from 3 unrelated families reported in literature, with 2 different homozygous variants in STT3A, as well as an additional case indicated by expert reviewer.

Created: 15 Oct 2020, 3:22 p.m. | Last Modified: 15 Oct 2020, 3:22 p.m.

Panel Version: 2.16

Green List (high evidence)

New MOI

PMID: 34653363 - 16 patients from 9 families with new AD mode of inheritance (both de novo and inherited). All variants were missense within/around acritical active/catalytic sites. Patients aged 3-55yo, with children noted to be "healthy" until reaching young adulthood
Clinical features include dysmorphic features, macrocephaly (6/16), mild-moderate ID/DD (10/16), short stature (8/16), skeletal abnormalities (10/16), muscle cramps (7/16).
Functional studies verifies AR disease is caused by LOF variants, whereas the AD variants cause DN proven by cotransfection in WT yeast resulting in impaired glycosylation (protein levels unchanged).

Created: 4 Dec 2021, 8:01 a.m. | Last Modified: 4 Dec 2021, 8:01 a.m.

Panel Version: 2.78

Bi-allelic variants: Three families reported to date.

Created: 22 Jul 2020, 9:55 a.m. | Last Modified: 4 Dec 2021, 8:01 a.m.

Panel Version: 2.78

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Iw; OMIM #615596

Publications

• 23842455
• 30701557
• 28424003
• 34653363

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

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 11:11 a.m. | Last Modified: 3 Mar 2022, 11:17 a.m.

Panel Version: 2.80

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. One published variant reported and expert reviewer reported an additional variant.

Created: 19 Dec 2016, 2:55 p.m.

Green List (high evidence)

only one patient described in the literature, but I do know of a second patient being treated in the UK.

Created: 12 Dec 2016, 2:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 23842455