Infantile Hypertrophic Cardiomyopathy Associated with a Novel <b><i>MYL3</i></b> Mutation

Abstract

Mutations in genes encoding cardiac sarcomeric proteins are thought to be a very rare cause of hypertrophic cardiomyopathy (HCM) in infants and young children. We report on genetic and histopathological findings in a 3-month-old infant presenting with severe progressive HCM arising from a mutation in the gene encoding the essential light chain of myosin (MYL3). The patient was found to have a novel, paternally inherited pathogenic c.530 A>G mutation in exon 5 of the MYL3 gene. His father was asymptomatic. Although, MYL3 mutations have been previously associated with adult-onset HCM, it has not been seen in infantile forms. As such, this case adds to the emerging evidence demonstrating that familial disease associated with mutations in cardiac sarcomere protein genes may have an important role in infants and children with HCM. In addition, this case highlights the marked phenotypic heterogeneity associated with sarcomeric protein mutations both within and between families.

The genetic basis of hypertrophic cardiomyopathy in cats and humans

“…In an Amish population, individuals homozygous for mutations in MYBPC3 also develop severe infantile HCM. 67,68 …”

Gene Co-Expression Network Analysis Provides Novel Insights into Myostatin Regulation at Three Different Mouse Developmental Timepoints

“…A recent report demonstrated that BMP8B directly regulates thermogenesis in brown adipose tissues [ 52 ], which indicates that MSTN may alter adipose metabolism through BMP8B. In addition, recent research identified a mutation in Myl3 that can cause hypertrophic cardiomyopathy in infants [ 53 ]. In our study, over 4,000 genes were differentially hubbed with Myl3 in wild-type compared to MSTN-null mice.…”

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

“…Another significant difference between ToF and ASD transcriptomes was related to the enrichment of sarcomeric protein-coding genes in ASD atrial samples. Although only MYL3 dysregulation has been previously linked to ASD pathogenesis [16], ACTA1 and MURC overexpression was reported to contribute to cardiac contractile dysfunction and conduction disturbances in mouse models [44,45], whereas MYL3, MURC, and MYH11 gene mutations or copy number variants were found associated with cardiomyopathy or CHDs [46][47][48]. Based on this evidence, we hypothesize that the observed upregulation of contractile fiber genes in the ASD myocardium and functional interactions among their products, predicted by network analysis, are critical for disease development.…”