Palmoplantar keratoderma and erythrokeratodermas
Gene: GJB4
Lots of literature on GJB4 as a causative gene in EKVCreated: 14 Mar 2017, 7:17 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Erythrokeratoderma variabilis
Comment on phenotypes: Removed 'Erythrokeratodermia variabilis with erythema gyratum repens,133200' as a phenotype since a June 2017 OMIM update now associates GJB4 with 'Erythrokeratodermia variabilis et progressiva 2, 617524'.Created: 15 Aug 2017, 2:19 p.m.
Comment when marking as ready: Discussed with Helen Brittain, who agrees with Green rating and monoallelic MOI (cases reported for GJB4 are heterozygous).Created: 3 Apr 2017, 9:12 a.m.
Comment on list classification: Updated rating from Amber to green: 1 green review plus >3 cases supporting causation for 'Erythrokeratodermia variabilis et progressiva'.Created: 16 Mar 2017, 4:29 p.m.
Although GJB4 is not a confirmed DD gene for EKVP (OMIM:133200) >3 GJB4 cases listed in OMIM for 'Erythrokeratodermia variabilis et progressiva (OMIM:133200)' and plenty of literature recording GJB4 causative variants for OMIM:133200.Created: 16 Mar 2017, 4:07 p.m.
Comment on list classification: Updated rating from Red to Amber ready for External review: >3 cases linking GJB4 to EKVP (OMIM:133200).Created: 10 Jan 2017, 3:39 p.m.
Comment on mode of inheritance: Updated mode of inheritance from 'Both monoallelic and biallelic' to just monoallelic. Although OMIM report both biallelic and monoallelic causes of EKVP (OMIM:133200) for GJA1, GJB3 and GJB4, for GJB4 the literature reports heterozygous (monoallelic) mutations. Rare biallelic forms of EKVP (OMIM:133200) have so far just been reported for GJB3.Created: 10 Jan 2017, 3:38 p.m.
Comment on mode of inheritance: Mode of inheritance sourced from OMIM: Both monoallelic and biallelic mutations in GJB4 are recorded for Erythrokeratodermia variabilis with erythema gyratum repens' (OMIM:133200).Created: 5 Jan 2017, 1:20 p.m.
Phenotypes for gene: GJB4 were changed from Erythrokeratodermia variabilis et progressiva 2, 617524 to Erythrokeratodermia variabilis et progressiva 2, OMIM:617524
Phenotypes for GJB4 were set to Erythrokeratodermia variabilis et progressiva 2, 617524
Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Mode of inheritance for GJB4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for GJB4 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
GJB4 was created by rfoulger
GJB4 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Radboud University Medical Center, Nijmegen