Paediatric or syndromic cardiomyopathy

Gene: PKD2

Green List (high evidence)

Comment on list classification: There are patients from five unrelated families reported with five different heterozygous PKD2 variants and with cardiomyopathy. Of these, four families were from APKD2 database at Mayo Clinic and one was from the UK 100,000 genomes cohort. There is also functional evidence available from zebrafish and mice model. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 7 Sep 2025, 10:08 p.m. | Last Modified: 7 Sep 2025, 10:08 p.m.

Panel Version: 7.86

Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025).

Reports on human patients:
PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G.

PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene (p.Arg213Ter) via analysis of data from singleton genome sequencing.

Functional studies:

PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants.

PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy.
Sources: Literature

Created: 7 Sep 2025, 10:02 p.m. | Last Modified: 7 Sep 2025, 10:04 p.m.

Panel Version: 7.85

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Polycystic kidney disease 2, OMIM:613095; polycystic kidney disease 2, MONDO:0013131; dilated cardiomyopathy, MONDO:0005021

Publications

• 23376035
• 27081851
• 29270497
• 39472908