Palmoplantar keratoderma and erythrokeratodermas

Gene: KRT6B

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pachyonychia congenita

Publications

• 9618173
• 16250204

Comment when marking as ready: 1 Green review plus KRT6B is listed in the 'Eligibility statement, Prior Genetic Testing'. 3 cases (from 2 papers) based on 1 variant linking KRT6B to Pachyonychia congenita.

Created: 10 Jan 2017, 5:10 p.m.

Comment on list classification: Updated rating from Amber to Green: One green review plus KRT6B is included in the Eligibility statement 'Prior Genetic Testing' list. 1 Variant listed in OMIM for 3 families. Not yet a confirmed DD gene.

Created: 9 Jan 2017, 12:12 p.m.

In 2 families (families 29 and 30) segregating pachyonychia congenita, Smith et al. (2005, PMID:16250206) identified heterozygosity for the same E472K mutation in the KRT6B gene that had been identified in a Dutch family in their earlier paper (Smith et al.,1998, PMID:9618173). Haplotype analysis showed that family 29 had an independent occurrence of the mutation; haplotype analysis was not possible in family 30 because of lack of samples, but the family was not of Dutch ancestry.

Created: 5 Jan 2017, 4:44 p.m.

In a family with autosomal dominant pachyonychia congenita (PC4; 615728), Smith et al. (PMID:9618173, 1998) described a heterozygous 1459G-A mutation in KRT6B that predicted a glu472-to-lys (E472K) substitution. The clinical features pictured included focal palmoplantar keratoderma.

Created: 5 Jan 2017, 4:43 p.m.

Comment on publications: PMID:9618173 (Smith et al., 1998) reports that a mutation in KRT6B produces a phenocopy of the K17 disorder pachyonychia congenita type 2 (PC-2).

Created: 5 Jan 2017, 4:35 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.

Created: 5 Jan 2017, 4:30 p.m.