Early onset or syndromic epilepsy

Gene: PRMT9

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (>10 unrelated families) for the association of biallelic PRMT9 variants with epilepsy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 9 Jan 2026, 2:24 p.m. | Last Modified: 9 Jan 2026, 2:24 p.m.

Panel Version: 8.90

PMID:41260215 (2025) reported the identification of biallelic loss-of-function variants in PRMT9 gene in 35 individuals from 26 unrelated families primarily presenting with a neurodevelopmental disorder characterised by global developmental delay, learning disabilities, mild to severe intellectual disability, autism spectrum disorder, epilepsy, and hypotonia.

There were 26 different variants identified in total which included frameshifting indels, nonsense variants, missense variants, and two copy-number variants.

Clinical examinations revealed that 14 individuals developed epilepsy, which was suspected in one other individual.

Functional evidence available from skin fibroblasts derived from affected individuals showed reduced expression at the RNA and/or protein level and subsequent aberrant methylation activity. Transcriptomic analysis of fibroblasts from affected individuals indicated differential expression of genes related to intellectual disability, autism, and cilia, suggesting a role of PRMT9 during ciliogenesis. Under ciliogenesis conditions, the skin-derived fibroblasts exhibited anomalies in the length of primary cilia but normal amounts of cilia. In addition, a prmt9 knockout zebrafish model displayed abnormal social preference in adult animals.

This gene has not yet been associated with relevant phenotypes in OMIM (last accessed 09 January 2026), but has been associated with 'Limited' rating on the DD panel in Gene2Phenotype.
Sources: Literature

Created: 9 Jan 2026, 2:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41260215