Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation

Angela M. Kelle, S. Jared Bentley, Luis O. Rohena, Allison K. Cabalka, Timothy Mark Olson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Ebstein anomaly of the tricuspid valve (EA) can be associated with left ventricular non-compaction (LVNC), a rare congenital cardiomyopathy. We report a 2 year-old female with EA and severe tricuspid regurgitation, LVNC, pulmonary hypertension, and chronic biventricular systolic heart failure, who died during evaluation for cardiac transplantation. Gene panel testing revealed a heterozygous de novo missense mutation in TPM1, which encodes the cardiac sarcomeric thin filament protein α-tropomyosin. The c.475G>A variant results in a p.Asp159Asn substitution, altering a highly conserved residue predicted to be damaging to protein structure and function. TPM1 is the second gene linked to EA with LVNC in humans, implicating overlap in the molecular basis of structural and myopathic heart disease.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - 2016

Fingerprint

Ebstein Anomaly
Tropomyosin
Heart Failure
Systolic Heart Failure
Tricuspid Valve Insufficiency
Mutation
Tricuspid Valve
Missense Mutation
Heart Transplantation
Cardiomyopathies
Pulmonary Hypertension
Genes
Heart Diseases
Proteins

Keywords

  • Cardiomyopathy
  • Congenital heart defects
  • Ebstein anomaly
  • Genetic testing
  • Genetics
  • Heart failure
  • Left ventricular noncompaction
  • Mutation
  • TPM1
  • Tropomyosin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation. / Kelle, Angela M.; Bentley, S. Jared; Rohena, Luis O.; Cabalka, Allison K.; Olson, Timothy Mark.

In: American Journal of Medical Genetics, Part A, 2016.

Research output: Contribution to journalArticle

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abstract = "Ebstein anomaly of the tricuspid valve (EA) can be associated with left ventricular non-compaction (LVNC), a rare congenital cardiomyopathy. We report a 2 year-old female with EA and severe tricuspid regurgitation, LVNC, pulmonary hypertension, and chronic biventricular systolic heart failure, who died during evaluation for cardiac transplantation. Gene panel testing revealed a heterozygous de novo missense mutation in TPM1, which encodes the cardiac sarcomeric thin filament protein α-tropomyosin. The c.475G>A variant results in a p.Asp159Asn substitution, altering a highly conserved residue predicted to be damaging to protein structure and function. TPM1 is the second gene linked to EA with LVNC in humans, implicating overlap in the molecular basis of structural and myopathic heart disease.",
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