Why the study?
Intellectual disability with developmental delay is rarely associated with congenital cardiomyopathy.
Does a CAMK2D de novo missense variant cause syndromic neurodevelopmental disorder with dilated cardiomyopathy?
Does a CAMK2D de novo missense variant cause syndromic neurodevelopmental disorder with dilated cardiomyopathy?
The CaMKIIδ Arg275His missense variant is identified as a probable cause of a syndromic neurodevelopmental disorder presenting with dilated cardiomyopathy.
Suggests CAMK2D testing in syndromic dilated cardiomyopathy; leaves open causality pending replication and functional studies.
BACKGROUND: Intellectual disability with developmental delay is the most common developmental disorder. However, this diagnosis is rarely associated with congenital cardiomyopathy. In the current report, we present the case of a patient suffering from dilated cardiomyopathy and developmental delay. METHODS: Neurological pathology in a newborn was diagnosed immediately after birth, and the acquisition of psychomotor skills lagged behind by 3-4 months during the first year of life. WES analysis of the proband did not reveal a causal variant, so the search was extended to trio. RESULTS: /calmodulin-dependent protein kinase II delta (CaMKIIδ) protein is known to be increased in the heart tissues from patients with dilated cardiomyopathy. The functional effect of the CaMKIIδ Arg275His mutant was recently reported; however, no specific mechanism of its pathogenicity was proposed. A structural analysis and comparison of available three-dimensional structures of CaMKIIδ confirmed the probable pathogenicity of the observed missense variant. CONCLUSIONS: We suggest that the CaMKIIδ Arg275His variant is highly likely the cause of dilated cardiomyopathy and neurodevelopmental disorders.
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Tolmacheva et al. (2023) studied this question.
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