Genetic Epilepsy

Gene: SLC35A2

Green List (high evidence)

Association with CDG: Summary: gene-disease association is well-established. 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.

Association with MOGHE: 9 individuals reported with somatic variants.

Created: 23 Mar 2021, 3:49 a.m. | Last Modified: 23 Mar 2021, 3:49 a.m.

Panel Version: 0.6857

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) 30817854; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)

Publications

• 23561849
• 24115232
• 27743886
• 25778940
• 33407896