Congenital disorders of glycosylation

Gene: SLC35A2

Green List (high evidence)

The rating of this gene has been updated to Green 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

Green List (high evidence)

Gene-disease association is well-established, XLD inheritance, mosaicism in males. Phenotypes are mostly CNS related (epilepsy, dev delay, etc). Only a minority have abnormal transferrin glycosylation (10/53 reported individuals according to PMID: 30817854). 3 unrelated individuals with de novo variants reported in PMID:23561849, 2 males and 1 female. The males were mosaic. "In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement." 4 unrelated girls with de novo variants and early onset epileptic encephalopathy reported in PMID:24115232 and PMID:27743886. None showed abnormal glycosylation although 'favourable X-inactivation skewing' was noted for some. One more girl with a de novo variant and defective galactosylation of N‐glycans, developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment was described in PMID:25778940. PMID:30817854 describes another 30 individuals with de novo variants. Only 1 was male (not apparently mosaic), and only 4 had abnormal carbohydrate deficient transferrin.

Created: 22 Jul 2020, 6:12 a.m. | Last Modified: 22 Jul 2020, 6:12 a.m.

Panel Version: 2.14

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Congenital disorder of glycosylation, type IIm (MIM #300896)

Publications

• 23561849
• 24115232
• 27743886
• 25778940
• 30817854

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

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 8 Feb 2021, 5:05 p.m. | Last Modified: 8 Feb 2021, 5:05 p.m.

Panel Version: 2.62

Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least 3 variants reported, as hemizygous in two males and mononallelic in another.

Created: 19 Dec 2016, 2:04 p.m.

Green List (high evidence)

Can be a mosaic mutation in males

Created: 14 Dec 2016, 2:21 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 25778940
• 27743886
• 23561849