Early onset or syndromic epilepsy

Gene: ANO4

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 10:58 a.m. | Last Modified: 26 Sep 2024, 10:58 a.m.

Panel Version: 6.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

To date, no phenotype has been associated with ANO4 variants in OMIM, Gen2Phen or Mondo.

Created: 3 Jun 2024, 4:21 p.m. | Last Modified: 3 Jun 2024, 4:21 p.m.

Panel Version: 5.13

PMID: 38744284 reports five de novo ANO4 missense variants in patients (I1–I5) with a phenotype that includes intellectual disability, developmental and epileptic or epileptic encephalopathy (DEE/EE) and hypotonia. A further two ANO4 missenses variants were observed, one had been inherited from unaffected mother (patient F7) and with a penetrance of 73% in members of a large pedigree with a milder phenotype (PMID: 38744284: Supplementary figure S2). Febrile seizures plus (GEFS+) or temporal lobe epilepsy were associated with these inherited variants. A dominant negative mechanism was proposed by Yang et al (PMID: 38744284) as a result of functional studies of one of the variants causing DEE/EE and one causing GEFS+.
Sources: Literature

Created: 3 Jun 2024, 3:47 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 38744284

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments