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Hwang JW, Jang MA, Jang SY, et al. Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation. Korean Circ J. 2017;47(2):270-277doi: 10.4070/kcj.2016.0213.
Hwang, J. W., Jang, M. A., Jang, S. Y., Seo, S. H., Seong, M. W., Park, S. S., Ki, C. S., & Kim, D. K. (2017). Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation. Korean circulation journal, 47(2), 270-277. https://doi.org/10.4070/kcj.2016.0213
Hwang, Ji-Won, et al. "Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation." Korean circulation journal vol. 47,2 (2017): 270-277. doi: https://doi.org/10.4070/kcj.2016.0213
Hwang JW, Jang MA, Jang SY, Seo SH, Seong MW, Park SS, Ki CS, Kim DK. Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation. Korean Circ J. 2017 Mar;47(2):270-277. doi: 10.4070/kcj.2016.0213. Epub 2017 Mar 13. PMID: 28382084; PMCID: PMC5378035.
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Korean Circ J. 2017 Mar;47(2):270-277. doi: 10.4070/kcj.2016.0213. Epub 2017 Mar 13.

Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation.

Korean circulation journal

Ji-Won Hwang, Mi-Ae Jang, Shin Yi Jang, Soo Hyun Seo, Moon-Woo Seong, Sung Sup Park, Chang-Seok Ki, Duk-Kyung Kim

Affiliations

  1. Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  2. Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.
  3. Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  4. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

PMID: 28382084 PMCID: PMC5378035 DOI: 10.4070/kcj.2016.0213

Abstract

Genetic diagnosis of cardiomyopathies is challenging, due to the marked genetic and allelic heterogeneity and the lack of knowledge of the mutations that lead to clinical phenotypes. Here, we present the case of a large family, in which a single TNNI3 mutation caused variable phenotypic expression, ranging from restrictive cardiomyopathy (RCMP) to hypertrophic cardiomyopathy (HCMP) to near-normal phenotype. The proband was a 57-year-old female with HCMP. Examining the family history revealed that her elder sister had expired due to severe RCMP. Using a next-generation sequencing-based gene panel to analyze the proband, we identified a known TNNI3 gene mutation, c.433C>T, which is predicted to cause an amino acid substitution (p.Arg145Trp) in the highly conserved inhibitory region of the cardiac troponin I protein. Sanger sequencing confirmed that six relatives with RCMP or near-normal phenotypes also carried this mutation. To our knowledge, this is the first genetically confirmed family with diverse phenotypic expression of cardiomyopathies in Korea. Our findings demonstrate familial implications, where a single mutation in a sarcomere protein can cause diverse phenotypic expression of cardiomyopathies.

Keywords: Cardiomyopathies; Cardiomyopathy, hypertrophic; Cardiomyopathy, restrictive; Korean; TNNI3 mutation

Conflict of interest statement

The authors have no financial conflicts of interest.

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