Ichthyosis and erythrokeratoderma

Gene: DSC2

Green List (high evidence)

Comment when marking as ready: Discussed with Helen Brittain, and green rating agreed.

Created: 3 Apr 2017, 9:04 a.m.

Comment on list classification: After discussion with Helen Brittain, kept rating as Green: The desmosomal genes are included in the eligibility statement "Striate keratoderma with woolly hair: cardiac panel including desmosomal genes", and (unlike DES and DSG2) DSC2 is linked to the keratoderma phenotype. Although there is borderline number of cases (3 patients, 2 families), the phenotype is in-keeping with the role of the gene product in cell:cell adhesion. Therefore, Helen agrees that the rating should be Green for biallelic cases.

Created: 3 Apr 2017, 9:02 a.m.

Comment on mode of inheritance: Recorded mode of inheritance as 'Biallelic' to match reviewer suggestion: Although OMIM records both biallelic and monoallelic DSC2 mutations for 'Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair' (OMIM:610476), the reported cases (PMID:18957847 and PMID:23863954) identify homozygous mutations. Heterozygous mutations are noted for 'Arrhythmogenic right ventricular dysplasia 11' (also OMIM:610476) but these don't include the relevant PPK phenotype.

Created: 10 Jan 2017, 2:32 p.m.

Comment on list classification: Updated rating from Amber to Green: DSC2 is included in the 'Prior genetic testing' list of the Eligibility statement. Only 2 papers (PMID:18957847 with 2 siblings, and PMID:23863954 where one individual is reported with mild palmoplantar hyperkeratosis).

Created: 10 Jan 2017, 2:19 p.m.

In PMID:23863954 (2013), Gerull et al., identified homozygosity for a nonsense mutation in the DSC2 gene (c.1660C>T , Q554X) in 6 affected individuals from 2 Canadian Hutterite kindreds with ARVC that segregated fully with disease in both families. Mild palmoplantar hyperkeratosis was observed in one of the Canadian patients, who had normal hair.

Created: 5 Jan 2017, 4:58 p.m.

Comment on publications: PMID:18957847 (Simpson et al., 2009) report 2 Pakistani siblings who present with arrhythmogenic right ventricular cardiomyopathy (ARVC) and associated mild palmoplantar keratoderma and woolly hair. Sequence analysis revealed a homozygous single-base deletion in exon 12 (1841delG). This mutation is predicted to lead to a frame shift and a premature termination codon at position 625 (S614fsX625). The unaffected first-cousin parents and an unaffected sister were heterozygous carriers of the mutation, which was not found in 300 control chromosomes.

Created: 5 Jan 2017, 4:53 p.m.

I don't know

Just one publication; 2 siblings

Created: 16 Nov 2015, 8 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiomyopathy, woolly hair and mild keratoderma

Publications

• 18957847