Segmental overgrowth disorders - Deep sequencing
Gene: GJA4Comment on list classification: New gene added by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to green at the next GMS panel update.
A recurrent GJA4 c.121G>T (p.Gly41Cys) somatic variant has been found in >50 individuals with cavernous venous malformation. Functional studies have shown this is a GoF variant that leads to formation of a hyperactive hemichannel.Created: 31 Jul 2023, 1:44 p.m. | Last Modified: 31 Jul 2023, 1:46 p.m.
Panel Version: 3.7
Multiple patients with shared phenotype and hot-spot Gly41Cys somatic gain of function mutation in 33912852.
Sources: Expert listCreated: 3 May 2023, 3:35 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Cutaneous and hepatic vascular lesions (no OMIM phenotype)
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag Q3_23_NHS_review was removed from gene: GJA4.
gene: GJA4 was added gene: GJA4 was added to Segmental overgrowth disorders - Deep sequencing. Sources: Expert Review Amber,Expert list Q3_23_promote_green, Q3_23_NHS_review, recurrent-variant tags were added to gene: GJA4. Mode of inheritance for gene: GJA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GJA4 were set to 33912852; 35642047; 35902510; 36209871; 37072338 Phenotypes for gene: GJA4 were set to Cutaneous and hepatic vascular lesions (no OMIM phenotype) Penetrance for gene: GJA4 were set to unknown Mode of pathogenicity for gene: GJA4 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments