Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy.
Marta W SzulikMiguel Reyes-MugicaDaniel F MarkerAna M GomezMatthew D ZinnLeslie K WalshJuan Pablo OchoaSarah FranklinLina Ghaloul-GonzalezPublished in: Genes (2023)
Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous MYBPC3 variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the SMYD1 gene. The second patient, the proband's sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous MYBPC3 variant. While this specific MYBPC3 variant (c.1224-52G>A, IVS13-52G>A) has been previously reported to be associated with adult-onset hypertrophic cardiomyopathy, this is the first report linking it to infantile cardiomyopathy. In addition, this work describes, for the first time, a novel SMYD1 variant (c.302A>G; p.Asn101Ser) that has never been reported. We performed a histopathological evaluation of tissues collected from both probands and show that these variants lead to myofibrillar disarray, reduced and irregular mitochondrial cristae and cardiac fibrosis. Together, these results provide critical insight into the molecular functionality of these genes in human cardiac physiology.
Keyphrases
- hypertrophic cardiomyopathy
- left ventricular
- heart failure
- genome wide
- cardiac resynchronization therapy
- copy number
- bioinformatics analysis
- genome wide identification
- case report
- endothelial cells
- gene expression
- oxidative stress
- genome wide analysis
- early onset
- transcription factor
- induced pluripotent stem cells
- dna methylation