Ichthyosis and erythrokeratodermaGene: KRT6C
Targeted sequencing through PC Project
Created: 14 Mar 2017, 6:50 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Focal keratoderma; dystrophic nails
Mode of pathogenicity
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of pathogenicity: Kept mode-of-pathogenicity as 'Other' based on comment from Edel O'Toole: Keratin mutations are generally thought to be dominant negative.
Created: 11 Apr 2017, 1:02 p.m.
Comment on mode of inheritance: Mode of inheritance sourced from OMIM.
Created: 9 Jan 2017, 4:39 p.m.
Comment on list classification: Updated rating from Red to green: Not a confirmed DD gene, but 3 variants listed in OMIM (all from same 2010 publication: PMID:19609311) and KRT6C is listed for Prior genetic testing in the Eligibility statement.
Created: 9 Jan 2017, 4:38 p.m.
In 3 affected members of a Japanese family with focal or diffuse palmoplantar keratoderma (PPKNEFD; OMIM: 615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a c.1414G-A transition in exon 7 of the KRT6C gene, resulting in a E472K substitution. The same E472K mutation was found in a father and daughter with focal plantar keratoderma (and not in an unaffected son) by Kubo et al. (2013, PMID:23662636); palmar skin as well as the nails of hands and feet were normal in the affected individuals.
Created: 9 Jan 2017, 4:36 p.m.
In affected members of a 4-generation family with focal palmoplantar keratoderma (PPKNEFD; OMIM:615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a 27-bp deletion (c.1384_1410del27) in exon 7 of KRT6C . This mutation resulted in an in-frame deletion (Ile462_Glu470del).
Created: 9 Jan 2017, 4:34 p.m.
In a father and son in 1 family as well as the affected members of an unrelated 4-generation family with focal palmoplantar keratoderma (PPKNEFD; OMIM:615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a 3-bp deletion (c.516_518delCAA) in exon 1 of the KRT6C gene, resulting in an in-frame deletion (Asn172del). The mutation segregated with disease in both families; however, the 3-bp deletion was also present in 3 of 335 population controls.
Created: 9 Jan 2017, 4:33 p.m.
gene: KRT6C was added gene: KRT6C was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: KRT6C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRT6C were set to 19609311 Phenotypes for gene: KRT6C were set to Focal keratoderma; Palmoplantar keratoderma, nonepidermolytic, focal or diffuse, 615735; dystrophic nails Mode of pathogenicity for gene: KRT6C was set to Other - please provide details in the comments