title: Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation.
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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kelle
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, San Antonio Military Pediatric Center, Fort Sam Houston, Texas.
authors.forename: S Jared
authors.initials: SJ
authors.lastname: Bentley
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, San Antonio Military Medical Center, Fort Sam Houston, Texas.
authors.forename: Luis O
authors.initials: LO
authors.lastname: Rohena
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Cabalka
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.|Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Olson
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D004437:Ebstein Anomaly / Q000175:diagnosis / Q000235:genetics*; D004452:Echocardiography; D017809:Fatal Outcome; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010641:Phenotype; D013902:Radiography, Thoracic; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D014335:Tropomyosin
keywords: Ebstein anomaly; TPM1; cardiomyopathy; congenital heart defects; genetic testing; genetics; heart failure; left ventricular noncompaction; mutation; tropomyosin