Congenital disorders of glycosylation
Gene: SLC37A4
The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' 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 list classification: New gene added by Zornitza Stark (Australian Genomics). Monoallelic variants in SLC37A4 are linked to a congenital disorder of glycosylation in OMIM (MIM# 619525) and G2P (definitive disease confidence).
At least 9 individuals from 6 unrelated families have been reported with the same heterozygous variant, c.1267C>T (p.Arg423∗), in SLC37A4. Affected subjects display a metabolic disorder characterised by liver dysfunction, coagulation deficiencies (but no signs of bleeding detected in most), and profound abnormalities in N-glycosylation of serum specific proteins.Created: 16 Jun 2022, 1:21 p.m. | Last Modified: 16 Jun 2022, 1:21 p.m.
Panel Version: 2.84
PMID 33964207: 7 patients from 4 families, additional to the two reported previously, described with the same recurrent c.1267C>T (p.R423*) variant with liver dysfunction multifactorial coagulation deficiency and cardiac issues. Serum samples from affected individuals showed profound accumulation of both high mannose and hybrid type N-glycans. Hepatoma cell-line studies support the pathogenicity of the variant.Created: 11 Jun 2021, 8:34 a.m. | Last Modified: 11 Jun 2021, 8:34 a.m.
Panel Version: 2.70
Bi-allelic LOF variants in this gene cause glycogen storage disorder.
Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: LiteratureCreated: 2 Nov 2020, 10:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Congenital disorder of glycosylation
Publications
Tag Q3_22_rating was removed from gene: SLC37A4.
Source Expert Review Green was added to SLC37A4. Source NHS GMS was added to SLC37A4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: SLC37A4 were set to 32884905
Gene: slc37a4 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SLC37A4 were changed from Congenital disorder of glycosylation to Congenital disorder of glycosylation, type IIw, OMIM:619525
Tag Q3_22_rating tag was added to gene: SLC37A4.
gene: SLC37A4 was added gene: SLC37A4 was added to Congenital disorders of glycosylation. Sources: Literature Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC37A4 were set to 32884905 Phenotypes for gene: SLC37A4 were set to Congenital disorder of glycosylation Review for gene: SLC37A4 was set to RED