TY  - EJOU
AU  - Park, Junsung 
AU  - Seo, Go Hun 
AU  - Lee, Yena 
AU  - Choi, Yunha 
AU  - Kang, Minji 
AU  - Do, Hyo-Sang 
AU  - Kim, Young-Hwue 
AU  - Yu, Jeong Jin 
AU  - Kim, Ellen Ai-Rhan 
AU  - Jung, Euiseok 
AU  - Lee, Byong Sop 
AU  - Baek, Jae Suk 
AU  - Lee, Beom Hee 

TI  - High Prevalence of Genetic Alterations in Infantile-Onset Cardiomyopathy
T2  - Structural and Congenital Heart Disease

PY  - 2021
VL  - 16
IS  - 4
SN  - 3071-1738

AB  - <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.
KW  - Cardiomyopathy; whole exome sequencing; infantile-onset

DO  - 10.32604/CHD.2021.015167