Open Access

ARTICLE

High Prevalence of Genetic Alterations in Infantile-Onset Cardiomyopathy

by Junsung Park¹, Go Hun Seo², Yena Lee¹, Yunha Choi¹, Minji Kang³, Hyo-Sang Do³, Young-Hwue Kim⁴, Jeong Jin Yu⁴, Ellen Ai-Rhan Kim⁵, Euiseok Jung⁵, Byong Sop Lee⁵, Jae Suk Baek^4,#,*, Beom Hee Lee^1,6,#,*

1 Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2 3billion, Inc., Seoul, Korea
3 Genome Research Center for Birth Defects and Genetic Diseases, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
4 Division of Cardiology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5 Division of Neonatology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
6 Medical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

* Corresponding Authors: Jae Suk Baek. Email: ; Beom Hee Lee. Email:
# These authors contributed equally to this work

Congenital Heart Disease 2021, 16(4), 397-410. https://doi.org/10.32604/CHD.2021.015167

Received 27 November 2020; Accepted 23 December 2020; Issue published 19 April 2021

Abstract

Background and Method: 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. Result: 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. TPM1 and MYH7 variants were identified in the two patients with DCMP; MYH11 and MYLK2 variants in the two patients with LVNC; HRAS, BRAF, and MYH7 variants in three patients with HCMP; and MT-ND1 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 de novo, 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. Conclusion: 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.

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