@Article{CHD.2021.015167,
AUTHOR = {Junsung Park, Go Hun Seo, Yena Lee, Yunha Choi, Minji Kang, Hyo-Sang Do, Young-Hwue Kim, Jeong Jin Yu, Ellen Ai-Rhan Kim, Euiseok Jung, Byong Sop Lee, Jae Suk Baek, Beom Hee Lee},
TITLE = {High Prevalence of Genetic Alterations in Infantile-Onset Cardiomyopathy},
JOURNAL = {Structural and Congenital Heart Disease},
VOLUME = {16},
YEAR = {2021},
NUMBER = {4},
PAGES = {397--410},
URL = {http://www.techscience.com/schd/v16n4/42073},
ISSN = {3071-1738},
ABSTRACT = {<b>Background and Method:</b> The genetic cause of infantile-onset cardiomyopathy is rarely investigated. Here, we conducted whole exome sequencing (WES) and mitochondrial DNA (mtDNA) sequencing in eight patients with infantile-onset cardiomyopathy to identify genetic variations. <b>Result:</b> Among these patients, two (25%) had dilated cardiomyopathy (DCMP), two (25%) had left ventricular non-compaction (LVNC), and four (50%) had hypertrophic cardiomyopathy (HCMP). Except four patients identified prenatally, the remaining patients presented at a median age of 85.5 days. WES identified genetic variants in a total of seven (87.5%) patients and mtDNA sequencing in the other case. <i>TPM1</i> and <i>MYH7</i> variants were identified in the two patients with DCMP; <i>MYH11</i> and <i>MYLK2</i> variants in the two patients with LVNC; <i>HRAS, BRAF</i>, and <i>MYH7</i> variants in three patients with HCMP; and <i>MT-ND1</i> variant in one patient with HCMP having high blood lactic acid levels. Among the eight variants, four were classified as pathogenic or likely-pathogenic according to the American College of Medical Genetics (ACMG) guidelines, and the remaining were identified as variants of unknown significance (VUSs). Three pathogenic mutations were <i>de novo</i>, whereas four (likely-pathogenic or VUSs) were inherited from a respective parent, excluding one variant where parental testing was unavailable, questioning whether these inherited variants are disease-causing. Three patients died before 3 months of age. <b>Conclusion:</b> Genomic studies, such as WES with additional mtDNA sequencing, can identify a genetic variant in high proportions of patients with infantile-onset cardiomyopathy. The clinical implication of the parentally inherited variant needs to be assessed in a larger patient and family cohort with a longitudinal follow-up.},
DOI = {10.32604/CHD.2021.015167}
}