PUBLICATION
Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
- Authors
- Chetaille, P., Preuss, C., Burkhard, S., Côté, J.M., Houde, C., Castilloux, J., Piché, J., Gosset, N., Leclerc, S., Wünnemann, F., Thibeault, M., Gagnon, C., Galli, A., Tuck, E., Hickson, G.R., Amine, N.E., Boufaied, I., Lemyre, E., de Santa Barbara, P., Faure, S., Jonzon, A., Cameron, M., Dietz, H.C., Gallo-McFarlane, E., Benson, D.W., Moreau, C., Labuda, D., FORGE Canada Consortium, Zhan, S.H., Shen, Y., Jomphe, M., Jones, S.J., Bakkers, J., Andelfinger, G.
- ID
- ZDB-PUB-141006-1
- Date
- 2014
- Source
- Nature Genetics 46(11): 1245-9 (Journal)
- Registered Authors
- Bakkers, Jeroen
- Keywords
- none
- MeSH Terms
-
- Abnormalities, Multiple/genetics*
- Animals
- Arrhythmias, Cardiac/genetics*
- Arrhythmias, Cardiac/pathology
- Cell Cycle/genetics
- Cell Cycle Proteins/genetics*
- Chromosomal Proteins, Non-Histone/genetics*
- Enteric Nervous System/pathology
- Fibroblasts
- Founder Effect
- Gastrointestinal Tract/physiopathology
- Gene Knockdown Techniques
- Humans
- Intestinal Diseases/genetics*
- Intestinal Diseases/physiopathology
- Karyotyping
- Muscle Contraction/genetics
- Muscle Contraction/physiology*
- Muscle, Smooth, Vascular/pathology
- Mutation/genetics
- Quebec
- Signal Transduction/genetics*
- Syndrome
- Transforming Growth Factor beta/metabolism
- Zebrafish
- PubMed
- 25282101 Full text @ Nat. Genet.
- CTD
- 25282101
Citation
Chetaille, P., Preuss, C., Burkhard, S., Côté, J.M., Houde, C., Castilloux, J., Piché, J., Gosset, N., Leclerc, S., Wünnemann, F., Thibeault, M., Gagnon, C., Galli, A., Tuck, E., Hickson, G.R., Amine, N.E., Boufaied, I., Lemyre, E., de Santa Barbara, P., Faure, S., Jonzon, A., Cameron, M., Dietz, H.C., Gallo-McFarlane, E., Benson, D.W., Moreau, C., Labuda, D., FORGE Canada Consortium, Zhan, S.H., Shen, Y., Jomphe, M., Jones, S.J., Bakkers, J., Andelfinger, G. (2014) Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nature Genetics. 46(11):1245-9.
Abstract
The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-β signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping