Ectodermal Dysplasia

Gene: PRKD1

Green List (high evidence)

PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.

Created: 2 Oct 2020, 9:58 p.m. | Last Modified: 2 Oct 2020, 9:58 p.m.

Panel Version: 0.24

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital heart defects and ectodermal dysplasia, MIM# 617364

Publications

• 27479907
• 32817298

Green List (high evidence)

Only 3 pathogenic missense reported to date in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.

Created: 11 May 2020, 7:18 a.m. | Last Modified: 11 May 2020, 7:20 a.m.

Panel Version: 0.2790

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital heart defects and ectodermal dysplasia, 617364

Publications

• 27479907