Genes, Vol. 14, Pages 1177: CAMK2D De Novo Missense Variant in Patient with Syndromic Neurodevelopmental Disorder: A Case Report

Genes, Vol. 14, Pages 1177: CAMK2D De Novo Missense Variant in Patient with Syndromic Neurodevelopmental Disorder: A Case Report

Genes doi: 10.3390/genes14061177

Authors: Ekaterina R. Tolmacheva Jekaterina Shubina Taisiya O. Kochetkova Lubov’ V. Ushakova Ekaterina L. Bokerija Grigory S. Vasiliev Galina V. Mikhaylovskaya Ekaterina E. Atapina Nadezhda V. Zaretskaya Gennady T. Sukhikh Denis V. Rebrikov Dmitriy Yu. Trofimov

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: Trio sequencing revealed a de novo missense variant in the CAMK2D gene (p.Arg275His), that is, according to the OMIM database and available literature, not currently associated with any specific inborn disease. The expression of Ca2+/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.