| Literature DB >> 25282101 |
Philippe Chetaille1, Christoph Preuss2, Silja Burkhard3, Jean-Marc Côté1, Christine Houde1, Julie Castilloux1, Jessica Piché2, Natacha Gosset2, Séverine Leclerc2, Florian Wünnemann2, Maryse Thibeault2, Carmen Gagnon2, Antonella Galli4, Elizabeth Tuck4, Gilles R Hickson5, Nour El Amine5, Ines Boufaied5, Emmanuelle Lemyre5, Pascal de Santa Barbara6, Sandrine Faure6, Anders Jonzon7, Michel Cameron2, Harry C Dietz8, Elena Gallo-McFarlane8, D Woodrow Benson9, Claudia Moreau5, Damian Labuda5, Shing H Zhan10, Yaoqing Shen10, Michèle Jomphe11, Steven J M Jones10, Jeroen Bakkers3, Gregor Andelfinger12.
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.Entities:
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Year: 2014 PMID： 25282101 DOI： 10.1038/ng.3113
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330