Paediatric or syndromic cardiomyopathy

Gene: JAK1

I don't know

Comment on list classification: Monoallelic variants in JAK1 gene are primarily associated with 'Autoinflammation, immune dysregulation, and eosinophilia' (MIM #618999, accessed on 01 September 2025).

However, there is only one case from the UK 100,000 genomes cohort and functional evidence from mouse models in support of the association of monoallelic variants in this gene with dilated cardiomyopathy. Hence, this gene can only be rated amber with the current evidence.

Created: 1 Sep 2025, 11:05 a.m. | Last Modified: 1 Sep 2025, 11:05 a.m.

Panel Version: 7.50

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort. One of these patients with dilated cardiomyopathy was identified with de novo heterozygous missense variant in JAK1 gene (c.2666T>C/ p.Val889Ala) via reanalysis of data from trio genome sequencing, as this gene was not originally included in the panel. This variant was reported as likely pathogenic in the publication.

PMID:40744288 (2025) reported a mouse model with cardiomyocyte-specific deletion of JAK1, where JAK1 loss in cardiomyocytes results in dilated cardiomyopathy by 6 months of age, indicating cytokine receptor signaling through JAK1 is essential for cardiac physiology. In addition, cardiomyopathy in aged mice lacking cardiomyocyte JAK1 was characterised by substantial myocardial fibrosis.
Sources: Literature

Created: 1 Sep 2025, 11:01 a.m. | Last Modified: 1 Sep 2025, 11:28 a.m.

Panel Version: 7.50

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999; autoinflammation, immune dysregulation, and eosinophilia, MONDO:0033558; dilated cardiomyopathy, MONDO:0005021

Publications

• 39472908
• 40744288