RGD Reference Report - Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease. - Rat Genome Database

RGD Reference Report - Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease. - Rat Genome Database

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Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease.
Authors:	Massadeh, Salam Albeladi, Maha Albesher, Nour Alhabshan, Fahad Kampe, Kapil Dev Chaikhouni, Farah Kabbani, Mohamed S Beetz, Christian Alaamery, Manal
Citation:	Massadeh S, etal., Genes (Basel). 2021 Apr 21;12(5):612. doi: 10.3390/genes12050612.
RGD ID:	329322879
Pubmed:	PMID:33919081 (View Abstract at PubMed)
PMCID:	PMC8143129 (View Article at PubMed Central)
DOI:	DOI:10.3390/genes12050612 (Journal Full-text)
Congenital heart defects (CHDs) are the most common types of birth defects, and global incidence of CHDs is on the rise. Despite the prevalence of CHDs, the genetic determinants of the defects are still in the process of being identified. Herein, we report a consanguineous Saudi family with three CHD affected daughters. We used whole exome sequencing (WES) to investigate the genetic cause of CHDs in the affected daughters. We found that all affected individuals were homozygous for a novel splice-altering variant (NM_001330069.1: c.265-1G>T) of PRKD1, which encodes a calcium/calmodulin-dependent protein kinase in the heart. The homozygous variant was found in the affected patients with Pulmonary Stenosis (PS), Truncus Arteriosis (TA), and Atrial Septal Defect (ASD). Based on the family's pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of PRKD1 to be identified with a link to CHDs, while all other previously described variants act dominantly. Interestingly, the father of the affected daughters was also homozygous for the variant, though he was asymptomatic of CHDs himself. Since both of his sisters had CHDs as well, this raises the possibility that the novel PRKD1 variant may undergo autosomal recessive inheritance mode with gender limitation. This finding confirms that CHD can be associated with both dominant and recessive mutations of the PRKD1 gene, and it provides a new insight to genotype-phenotype association between PRKD1 and CHDs. To our knowledge, this is the first report of this specific PRKD1 mutation associated with CHDs.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PRKD1	Human	congenital heart disease		IAGP		DNA:SNP:intron:c.265-1G>T (human)	RGD
Prkd1	Rat	congenital heart disease		ISO	PRKD1 (Homo sapiens)	DNA:SNP:intron:c.265-1G>T (human)	RGD
Prkd1	Mouse	congenital heart disease		ISO	PRKD1 (Homo sapiens)	DNA:SNP:intron:c.265-1G>T (human)	RGD

Genes (Rattus norvegicus)


Prkd1 (protein kinase D1)

Genes (Mus musculus)


Prkd1 (protein kinase D1)

Genes (Homo sapiens)


PRKD1 (protein kinase D1)