PUBLICATION
Mutations in TAX1BP3 cause Dilated Cardiomyopathy with Septo-Optic Dysplasia
- Authors
- Reinstein, E., Orvin, K., Tayeb-Fligelman, E., Stiebel-Kalish, H., Tzur, S., Pimienta, A.L., Bazak, L., Bengal, T., Cohen, L., Gaton, D.D., Bormans, C., Landau, M., Kornowski, R., Shohat, M., Behar, D.M.
- ID
- ZDB-PUB-150204-9
- Date
- 2015
- Source
- Human Mutation 36(4): 439-42 (Journal)
- Registered Authors
- Keywords
- Cardiomyopathy, Septooptic dysplasia, TAX1BP3, exome sequencing
- MeSH Terms
-
- Adolescent
- Adult
- Amino Acid Sequence
- Animals
- Cardiomyopathy, Dilated/diagnosis
- Cardiomyopathy, Dilated/genetics*
- Electrocardiography
- Exome
- Facies
- Female
- Gene Knockdown Techniques
- High-Throughput Nucleotide Sequencing
- Humans
- Intracellular Signaling Peptides and Proteins/chemistry
- Intracellular Signaling Peptides and Proteins/genetics*
- Male
- Models, Molecular
- Molecular Sequence Data
- Mutation*
- Optic Nerve Diseases/pathology
- Pedigree
- Phenotype
- Septo-Optic Dysplasia/diagnosis
- Septo-Optic Dysplasia/genetics*
- Syndrome
- Young Adult
- Zebrafish
- PubMed
- 25645515 Full text @ Hum. Mutat.
Citation
Reinstein, E., Orvin, K., Tayeb-Fligelman, E., Stiebel-Kalish, H., Tzur, S., Pimienta, A.L., Bazak, L., Bengal, T., Cohen, L., Gaton, D.D., Bormans, C., Landau, M., Kornowski, R., Shohat, M., Behar, D.M. (2015) Mutations in TAX1BP3 cause Dilated Cardiomyopathy with Septo-Optic Dysplasia. Human Mutation. 36(4):439-42.
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-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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping