Palmoplantar keratoderma and erythrokeratodermas
Gene: GJB2
Comment when marking as ready: Green rating agreed by Helen Brittain: cases found from 3 unrelated families with AD deafness and PPK. Helen notes that is possible that the mutational spectrum may be limited (to date, the mutations affect codons 59, 73 and 75).Created: 3 Apr 2017, 9:07 a.m.
Mode of inheritance is listed as monoallelic. Although biallelic GJB2 mutations have been reported with 'Deafness, autosomal recessive 1A (OMIM:220290)' OMIM:220290 does not present with keratodermas, and therefore the mode of inheritance is recorded only for GJB2 disorders relevant to this skin disorder panel.Created: 10 Jan 2017, 2:15 p.m.
GJB2 is a confirmed DD gene for 'palmoplantar keratoderma with deafness' (OMIM:148350), amongst other disorders.Created: 9 Jan 2017, 12:07 p.m.
3 GJB2 variants listed in OMIM for palmoplantar keratoderma with deafness (OMIM:148350): In a family with autosomal dominant deafness and palmoplantar keratoderma (OMIM:148350), Heathcote et al. (2000, PMID:10633135) identified a G-to-C transversion at nucleotide 175 of the GJB2 gene resulting in the substitution G59A. In a 4-generation Turkish family segregating for autosomal dominant deafness and palmoplantar keratoderma (148350), Uyguner et al. (2002, PMID:12372058) identified a 224G-A transition in the GJB2 gene resulting in an R75Q mutation. In a 40-year-old German woman and her 2 children with palmoplantar keratoderma and sensorineural deafness, de Zwart-Storm et al. (2008, PMID:17993581) identified heterozygosity for a mutation in the GJB2 gene (H73R).Created: 9 Jan 2017, 12:05 p.m.
Comment on list classification: Updated rating from Red to Green because GJB2 is included in the Eligibility statement gene list for 'Prior genetic testing' for patients with Keratoderma with deafness.Created: 9 Jan 2017, 11:56 a.m.
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).
Model of inheritance for gene GJB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
GJB2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Source: Radboud University Medical Center, Nijmegen
GJB2 was created by ellenmcdonagh
GJB2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Eligibility statement prior genetic testing