Palmoplantar keratoderma and erythrokeratodermas

Gene: DSC2

Green List (high evidence)

DSC2 (desmocollin 2)
EnsemblGeneIds (GRCh38): ENSG00000134755
EnsemblGeneIds (GRCh37): ENSG00000134755
OMIM: 125645, Gene2Phenotype
DSC2 is in 9 panels

3 reviews

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

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.

Edel O'Toole (Queen Mary University of London)

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Striate keratoderma with woolly hair
  • Arrhythmogenic right ventricular dysplasia 11, 610476
  • Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, 610476
OMIM
125645
Clinvar variants
Variants in DSC2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Apr 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

3 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

3 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

10 Jan 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for DSC2 was changed to BIALLELIC, autosomal or pseudoautosomal

10 Jan 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

5 Jan 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DSC2 were set to 18957847

5 Jan 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene DSC2 were set to Striate keratoderma with woolly hair; Arrhythmogenic right ventricular dysplasia 11, 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, 610476

5 Jan 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DSC2 were set to 18957847

27 Oct 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

DSC2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Source: UKGTN

27 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DSC2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Source: Radboud University Medical Center, Nijmegen

27 Oct 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

DSC2 was created by ellenmcdonagh

27 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

DSC2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Eligibility statement prior genetic testing, UKGTN