Congenital Heart Defect

Gene: PRKD1

I don't know

2 consanguineous families reported with homozygous variants for predicted to cause a loss of function (gene-disease association already established for autosomal dominant CHD due to de novo missense variants.)

PMID: 33919081: Three sisters with pulmonary stenosis, truncus arteriosis, and atrial septal defect were homozygous for c.265-1G>T. Their asymptomatic father was also homozygous, however he had two affected sisters (not genotyped), raising the possibility that PRKD1 may undergo autosomal recessive inheritance mode with gender limitation.

PMID: 25713110: Two sisters with truncus arteriosis were homozygous for R618X.

Created: 8 Jun 2021, 6:50 a.m. | Last Modified: 8 Jun 2021, 6:50 a.m.

Panel Version: 0.113

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autosomal Recessive Congenital Heart Disease

Publications

• 25713110
• 33919081

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, 9:50 p.m. | Last Modified: 2 Oct 2020, 9:58 p.m.

Panel Version: 0.70

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

Created: 11 May 2020, 11:03 a.m. | Last Modified: 11 May 2020, 11:03 a.m.

Panel Version: 0.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital heart defects and ectodermal dysplasia, 617364

Publications

• 27479907
• 32817298