Ichthyosis and erythrokeratoderma

Gene: GJB3

Comment on phenotypes: Previous phenotypes:
Erythrokeratoderma;deafness;Erythrokeratodermia variabilis et progressiva, 133200;peripheral neuropathy;Erythrokeratodermia Variabilis

Created: 23 Mar 2021, 2:30 p.m. | Last Modified: 23 Mar 2021, 2:30 p.m.

Panel Version: 1.28

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Erythrokeratoderma; deafness; peripheral neuropathy

Publications

• 9843209
• 10594760

Mode of pathogenicity
Other

Comment on list classification: Updated rating from Amber to Green: Although the reviewer did not leave a rating for GJB3, other comments were left suggesting that it is a suitable gene for the panel. >3 unrelated cases to support causation of relevant phenotype.

Created: 23 Mar 2017, 10:32 a.m.

Comment on list classification: Updated rating from Red to Amber ready for External review. Confirmed DD gene, and >3 cases of GJB3 variants linked to EKVP (OMIM:133200).

Created: 10 Jan 2017, 3:36 p.m.

Comment on mode of inheritance: Mode of inheritance sourced from OMIM: both monoallelic and biallelic mutations in GJB3 are recorded for 'Erythrokeratodermia variabilis et progressiva' (OMIM:133200). Biallelic (AR) mutations are reported in Gottfried et al., 2002 (PMID:12019212) and Fuchs-Telem et al, 2011 (PMID:21564177).

Created: 9 Jan 2017, 11:45 a.m.

Comment on publications: PMID:21564177 reports an autosomal recessive GJB3 mutation (c.G88A leading to a V30I substitution) causing Erythrokeratoderma variabilis (EKVP).

Created: 9 Jan 2017, 11:44 a.m.

GJB3 is a confirmed DD gene for 'Erythrokeratodermia variabilis et progressiva' (OMIM:133200).

Created: 9 Jan 2017, 11:30 a.m.

Gottfried et al. (2002, PMID:12019212) identified 3 Israeli siblings with an autosomal recessive (AR) migratory form of erythrokeratodermia variabilis et progressiva (EKVP; 133200) who were homozygous for a 101T-C transition in GJB3.

Created: 9 Jan 2017, 11:29 a.m.

Wigloss et al., (1999, PMID: 10594760) identified an R42P mutation in the GJB3 gene in a family with EKVP (OMIM:133200). Richard et al., 2000 (PMID:10798362) found the same heterozygous mutation as the cause of EKV in another family.

Created: 9 Jan 2017, 11:28 a.m.

Richard et al., (1998, PMID:9843209) identified heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S).

Created: 9 Jan 2017, 11:27 a.m.