Ichthyosis and erythrokeratoderma

Gene: GJB2

Comment on phenotypes: Previous phenotypes:
Hystrix-like ichthyosis with deafness, 602540;Keratoderma, palmoplantar, with deafness, 148350;Deafness, autosomal recessive 1A, 220290;Deafness, autosomal dominant 3A, 601544;Keratitis-ichthyosis-deafness syndrome, 148210;Vohwinkel syndrome, 124500;Keratoderma with deafness;Bart-Pumphrey syndrome, 149200

Created: 23 Mar 2021, 2:29 p.m. | Last Modified: 23 Mar 2021, 2:29 p.m.

Panel Version: 1.27

Green List (high evidence)

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.