title: Mutations in TAX1BP3 cause dilated cardiomyopathy with septo-optic dysplasia.
abstract: 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.
authors: The Raphael Recanati Genetic Institute, Rabin Medical Center, Israel; Sackler School of Medicine, Tel Aviv University, Israel.
authors: Eyal
authors: E
authors: Reinstein
authors: Katia
authors: K
authors: Orvin
authors: Einav
authors: E
authors: Tayeb-Fligelman
authors: Hadas
authors: H
authors: Stiebel-Kalish
authors: Shay
authors: S
authors: Tzur
authors: Allen L
authors: AL
authors: Pimienta
authors: Lily
authors: L
authors: Bazak
authors: Tuvia
authors: T
authors: Bengal
authors: Lior
authors: L
authors: Cohen
authors: Dan D
authors: DD
authors: Gaton
authors: Concetta
authors: C
authors: Bormans
authors: Meytal
authors: M
authors: Landau
authors: Ran
authors: R
authors: Kornowski
authors: Mordechai
authors: M
authors: Shohat
authors: Doron M
authors: DM
authors: Behar
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D004562:Electrocardiography; D059472:Exome; D019066:Facies; D005260:Female; D055785:Gene Knockdown Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009901:Optic Nerve Diseases / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D025962:Septo-Optic Dysplasia / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult; D015027:Zebrafish
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C421249:TAX1BP3 protein, human
keywords: Septo-optic dysplasia; TAX1BP3; cardiomyopathy; exome sequencing