Mutations in TAX1BP3 cause dilated cardiomyopathy with septo-optic dysplasia

Eyal Reinstein, Katia Orvin, Einav Tayeb-Fligelman, Hadas Stiebel-Kalish, Shay Tzur, Allen L. Pimienta, Lily Bazak, Tuvia Bengal, Lior Cohen, Dan D. Gaton, Concetta Bormans, Meytal Landau, Ran Kornowski, Mordechai Shohat, Doron M. Behar

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20 Scopus citations


We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo-optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β-catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development. The term hereditary cardiomyopathy has been applied to heritable forms of heart failure with identifiable inheritance patterns. Although many cardiomyopathies have a genetic basis, only a limited number of genes have been identified as disease loci. We describe a novel cardiomyopathy syndrome caused by mutations in TAX1BP3; a gene previously not connected to monogenic disorders, thus expanding the spectrum of hereditary cardiomyopathies and suggests that TAX1BP3 is essential for heart development.

Original languageEnglish
Pages (from-to)439-442
Number of pages4
JournalHuman Mutation
Issue number4
StatePublished - 1 Apr 2015
Externally publishedYes

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  • Cardiomyopathy
  • Exome sequencing
  • Septo-optic dysplasia
  • TAX1BP3


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