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Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia
Author(s) -
Reinstein Eyal,
Orvin Katia,
TayebFligelman Einav,
StiebelKalish Hadas,
Tzur Shay,
Pimienta Allen L.,
Bazak Lily,
Bengal Tuvia,
Cohen Lior,
Gaton Dan D.,
Bormans Concetta,
Landau Meytal,
Kornowski Ran,
Shohat Mordechai,
Behar Doron M.
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22759
Subject(s) - missense mutation , biology , zebrafish , dilated cardiomyopathy , mutation , genetics , cardiomyopathy , pdz domain , arrhythmogenic right ventricular dysplasia , dysplasia , wnt signaling pathway , point mutation , xenopus , gene , medicine , heart failure
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.