Early onset or syndromic epilepsy

Gene: WNK3

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.

Panel Version: 3.29

Comment on list classification: There is now enough evidence to promote this gene to Green at the next GMS review - at least 14 individuals from 6 unrelated families with variants in the WNK3 gene, of which at least 5 subjects (3 families) displayed seizures.

Created: 5 Jul 2022, 9:06 a.m. | Last Modified: 5 Jul 2022, 9:11 a.m.

Panel Version: 2.543

Kury et al. 2022 (PMID: 35678782) reported 14 males from 6 unrelated families with hemizygous variants (3 LOF and 3 missense, predicted pathogenic) in the WNK3 gene. All (14/14) had DD/ID and variable other associations including seizures (5/13), mild microcephaly (6/13, ranging -2 to -2.4 SD) and structural brain malformations (7/10). Heterozygous mothers were all asymptomatic.

Created: 5 Jul 2022, 8:10 a.m. | Last Modified: 5 Jul 2022, 8:10 a.m.

Panel Version: 3.1618

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

Phenotypes
Intellectual disability, MONDO:0001071

Publications

• 35678782

Red List (low evidence)

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

Red List (low evidence)

Listed as a candidate ID gene in PMID:26350204 (Grozeva et al., 2015) but the supporting article (PMID:18498374) reports a possible autism link, which is out of scope for this ID panel.

Created: 31 Oct 2017, 9:24 a.m.

Phenotypes
X_linked intellectual disability; XLID

Publications

• 26350204

Red List (low evidence)