Key result
Novel JPH2 mutation A405S causes basal septal hypertrophy and cardiomyocyte disarray consistent with HCM.
Why the study?
Does the novel JPH2 mutation A405S cause hypertrophic cardiomyopathy?
Does the novel JPH2 mutation A405S cause hypertrophic cardiomyopathy?
The novel JPH2 mutation A405S is causally linked to hypertrophic cardiomyopathy, specifically basal septal hypertrophy, as demonstrated in a transgenic mouse model.
Answers are grounded in this paper and cite their sources.
Supports JPH2 A405S causality in mouse HCM model; leaves open human validation and clinical translation.
BACKGROUND: signaling in a pro-hypertrophic manner. OBJECTIVES: To determine using a transgenic mouse model whether a JPH2 mutation found in a HCM patient is responsible for disease development. METHODS: variant were subjected to echocardiography, cardiac MRI, hemodynamic analysis, and histology. RESULTS: mutation, A405S, was identified in a genotype-negative proband with significant basal septal hypertrophy. Although initially underappreciated by traditional echocardiographic imaging, PKI mice with this JPH2 mutation (residue A399S in mice) were found to exhibit similar basal hypertrophy using a newly developed echo imaging plane, and this was confirmed using cardiac MRI. Histological analysis demonstrated cardiomyocyte hypertrophy and disarray consistent with HCM. CONCLUSIONS: Variant A405S is a novel HCM-associated mutation in JPH2 found in a proband negative for mutations in the canonical HCM-associated genes. Studies in the analogous mouse model demonstrated for the first time a causal link between a JPH2 defect and HCM. Moreover, novel imaging approaches identified subvalvular septal hypertrophy, specific findings also reported in the human JPH2 mutation carrier.
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Quick et al. (2017) studied Hypertrophic cardiomyopathy (HCM). JPH2 mutation A405S (A399S in mice) was evaluated on Disease development (basal septal hypertrophy, cardiomyocyte hypertrophy and disarray). The novel JPH2 mutation A405S (A399S in mice) causes basal septal hypertrophy and cardiomyocyte disarray consistent with hypertrophic cardiomyopathy.
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