Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy

Jamie O Yang; Hapet Shaybekyan; Yan Zhao; Xuedong Kang; Gregory A Fishbein; Negar Khanlou; Juan C Alejos; Nancy Halnon; Gary Satou; Reshma Biniwale; Hane Lee; Glen Van Arsdell; Stanley F Nelson; Marlin Touma; UCLA Clinical Genomics Center; UCLA Congenital Heart Defects-BioCore Faculty

doi:10.3389/fcvm.2021.798985

Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy

Front Cardiovasc Med. 2022 Jan 6:8:798985. doi: 10.3389/fcvm.2021.798985. eCollection 2021.

Authors

Jamie O Yang¹, Hapet Shaybekyan^{2

3}, Yan Zhao^{2

3}, Xuedong Kang^{2

3}, Gregory A Fishbein⁴, Negar Khanlou⁴, Juan C Alejos², Nancy Halnon², Gary Satou², Reshma Biniwale², Hane Lee^{4

5}, Glen Van Arsdell², Stanley F Nelson^{2

4

5

6}, Marlin Touma^{1

2

3

6

7

8

9}; UCLA Clinical Genomics Center; UCLA Congenital Heart Defects-BioCore Faculty

Affiliations

¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
² Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
³ Neonatal/Congenital Heart Laboratory, Cardiovascular Research Laboratory, University of California, Los Angeles, Los Angeles, CA, United States.
⁴ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁵ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Institute for Precision Health, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁷ Department of Pediatrics, David Geffen School of Medicine, Children's Discovery and Innovation Institute, University of California, Los Angeles, Los Angeles, CA, United States.
⁸ The Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁹ Eli and Edythe Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscles biopsies exhibited mitochondrial hyperplasia with decreased complex IV activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.

Keywords: COXPD3; TSFM; hypertrophic cardiomyopathy; mitochondrial cardiomyopathy; mitochondrial hyperplasia; whole exome sequencing.

Copyright © 2022 Yang, Shaybekyan, Zhao, Kang, Fishbein, Khanlou, Alejos, Halnon, Satou, Biniwale, Lee, Van Arsdell, Nelson, Touma, the UCLA Clinical Genomics Center and the UCLA Congenital Heart Defects-BioCore Faculty.

Publication types

Case Reports

Grants and funding

R01 HL153853/HL/NHLBI NIH HHS/United States