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


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
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@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} }