Palmoplantar keratodermas
Gene: DSC3The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 31 Jan 2023, 2:38 p.m. | Last Modified: 31 Jan 2023, 2:38 p.m.
Panel Version: 2.6
Comment on mode of inheritance: Only cases with homozygous variants have been reported, therefore it is recommended that the mode of inheritance is changed to Biallelic only following GMS review.Created: 14 Apr 2022, 4:54 p.m. | Last Modified: 14 Apr 2022, 4:54 p.m.
Panel Version: 1.14
In OMIM this gene is associated with Hypotrichosis and recurrent skin vesicles (OMIM:613102) with a autosomal recessive mode of inheritance.
Two cases reported, both with homozygous variants in the affected individuals.
PMID: 19765682 - Ayub et al 2009 - large consanguineous family from Afghanistan with 4 affected siblings with hypotrichosis and the appearance of recurrent skin vesicle formation. Sequence analysis following homozygosity mapping identified a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in DSC3.
PMID: 31790667 - Onoufriadis et al 2020 - boy from consanguineous Egyptian family with skin blistering and hypotrichosis. A homozygous nonsense mutation in DSC3 (c.2180T>G; p.Leu727*) was identified. The parents and unaffected sister were heterozygous for this variant.
PMID: 18682494 - Chen et al 2008 - mouse model shows that loss of Dsc3 function in the epidermis causes impaired cell-cell adhesion, leading to intra-epidermal blistering and telogen hair loss.Created: 14 Apr 2022, 4:53 p.m. | Last Modified: 14 Apr 2022, 5:22 p.m.
Panel Version: 1.14
This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: DSC3; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.Created: 28 Jan 2019, 10:47 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_22_MOI was removed from gene: DSC3.
Mode of inheritance for gene DSC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DSC3 were changed from Desmosomal disorders; Palmoplantar keratoderma, woolly hair to Desmosomal disorders; Palmoplantar keratoderma, woolly hair; Hypotrichosis and recurrent skin vesicles, OMIM:613102; hereditary hypotrichosis with recurrent skin vesicles, MONDO:0013136
Publications for gene: DSC3 were set to
Mode of inheritance for gene: DSC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q2_22_MOI tag was added to gene: DSC3.
Source London North GLH was added to DSC3.
gene: DSC3 was added gene: DSC3 was added to Palmoplantar keratodermas. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: DSC3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: DSC3 were set to Desmosomal disorders; Palmoplantar keratoderma, woolly hair