Mosaic skin disorders

Gene: PORCN

Comment on list classification: Added from PanelApp UK mosaic skin disorders panel

Created: 28 Apr 2023, 6:50 a.m. | Last Modified: 28 Apr 2023, 6:50 a.m.

Panel Version: 1.9

Green List (high evidence)

Well established gene associated with Focal Dermal Hypoplasia (FDH). Predominantly reported in females (male lethality).

PMID: 19309688 - 24 unrelated patients (21 female and 3 male) with focal dermal hypoplasia (FDH) were studied. A variety of variants (nonsense, splice site and missense) were identified while 3 cases with skewed X inactivation had microdeletions eliminating PORCN. The 3 male cases were shown to be a result of postzygotic mosaicism which was also identified in 2 female cases.

PMID: 17546030 - 10 of 15 confirmed with FDH were analysed and heterozygous (missense, nonsense, indels) mutations causative of FDH was identified. In 9 cases, variants weren't detected in parental samples. A mildy affected father of 1 case showed somatic mosaicism for this variant while they identified de novo mosaic mutations in 3 male FDH cases but not in their parents.
Sources: NHS GMS

Created: 5 Apr 2023, 2:51 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Focal dermal hypoplasia (MONDO:0010592; MIM#305600)

Publications

• 17546030
• 19309688

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments