Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.

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.

DOI: 10.1038/ng.3113
010002000201520162017
Citations per Year

931 Citations

Semantic Scholar estimates that this publication has received between 112 and 3,277 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Chetaille2014MutationsIS, title={Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.}, author={Philippe Chetaille and Christoph Preuss and Silja Burkhard and Jean-Marc C{\^o}t{\'e} and Christine Houde and Julie Castilloux and Jessica Pich{\'e} and Natacha Gosset and S{\'e}verine Leclerc and Florian W{\"{u}nnemann and Maryse Thibeault and Carmen Gagnon and Antonella Galli and Elizabeth Tuck and Gilles R Hickson and Nour El Amine and Ines Boufaied and Emmanuelle Lemyre and Pascal de Santa Barbara and Sandrine Faure and Anders Jonzon and Michel Cameron and Harry C Dietz and Elena Gallo-McFarlane and D Woodrow Benson and Claudia Moreau and Damian Labuda and Shing H Zhan and Yaoqing Shen and Mich{\`e}le Jomphe and Steven J M Jones and Jeroen Bakkers and Gregor Andelfinger}, journal={Nature genetics}, year={2014}, volume={46 11}, pages={1245-9} }