Early onset or syndromic epilepsy

Gene: GSPT2

Green List (high evidence)

Comment on list classification: There are now at least 5 unrelated male individuals reported with hemizygous missense variants in GSPT2 and a neurodevelopmental disorder. Three individuals presented with childhood-onset epilepsy. The variants were inherited from unaffected mothers. Hence, this gene can be promoted to Green on this panel, with MOI set to "X-LINKED: hemizygous mutation in males, biallelic mutations in females".

Created: 27 Oct 2026, 12:57 p.m. | Last Modified: 27 Oct 2026, 12:57 p.m.

Panel Version: 9.91

PMID: 41420488 Wei et al., 2026
Study reports 6 male individuals from 6 unrelated Chinese families (including 1 fetal case) carrying hemizygous missense variants in GSPT2 with intellectual disability, delayed speech and language development, autism spectrum disorder, epilepsy, or abnormal fetal neurodevelopment. Severe ID / learning disability & DD were present in 5/5 individuals. Variable brain malformations and seizures were reported in 3 probands. Seizure age of onset was 9 months to 7 years.
Functional evidence: Structural molecular modeling revealed significant deleterious effects of the identified variants. GSPT2 is preferentially enriched in the brain and cerebellum compared with other tissues. Transcriptomics revealed that GABAergic and calcium-signaling-related genes were significantly downregulated in GSPT2-deficient cells.

GSPT2 is not yet associated with a disease entity in OMIM (accessed 27th Oct 2026).
Sources: Literature

Created: 27 Oct 2026, 12:55 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41420488