Early onset or syndromic epilepsy
Gene: WNK3
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
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
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
Tag gene-checked was removed from gene: WNK3.
Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Tag gene-checked tag was added to gene: WNK3.
Tag Q3_22_rating was removed from gene: WNK3.
Source Expert Review Green was added to WNK3. Source NHS GMS was added to WNK3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: WNK3 was added gene: WNK3 was added to Genetic epilepsy syndromes. Sources: Expert Review Amber Q3_22_rating tags were added to gene: WNK3. Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: WNK3 were set to 26350204; 35678782 Phenotypes for gene: WNK3 were set to X-linked intellectual disability, MONDO:0100284 Penetrance for gene: WNK3 were set to Complete