Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, Salt Lake City, UT 84112, USA.
Division of Pediatric Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Genes (Basel). 2023 Mar 6;14(3):659. doi: 10.3390/genes14030659.
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 and genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the gene. The second patient, the proband's sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous variant. While this specific 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 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.
心脏基因的突变是婴儿型心肌病的主要原因之一。在这项研究中，我们报告了两个携带 和 基因变异的同胞兄妹的遗传发现。第一个患者是一名女性先证者，表现为肥厚型心肌病（HCM）和双心室心力衰竭，携带纯合截断 变体 c.1224-52G>A（IVS13-52G>A）和 基因中的一个新的纯合变体（c.302A>G；p.Asn101Ser）。第二个患者是先证者的兄弟，是一名男性婴儿，被诊断为肥厚型心肌病，携带相同的 基因纯合变体。虽然这种特定的 变体（c.1224-52G>A，IVS13-52G>A）以前被报道与成人发病的肥厚型心肌病有关，但这是第一个将其与婴儿型心肌病联系起来的报告。此外，这项工作首次描述了一个从未报道过的新的 变体（c.302A>G；p.Asn101Ser）。我们对两个先证者的组织进行了组织病理学评估，结果表明这些变体导致肌原纤维排列紊乱、减少和不规则的线粒体嵴以及心脏纤维化。总之，这些结果为这些基因在人类心脏生理学中的分子功能提供了重要的见解。
