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

Philippe Chetaille; Christoph Preuss; S.B. Burkhard; Jean Marc Cote; Christine Houde; Julie Castilloux; Jessica Piche; Natacha Gosset; Severine Leclerc; Florian Wuennemann; Maryse Thibeault; Carmen Gagnon; Antonella Galli; Elizabeth Tuck; Gilles R. Hickson; Nour El Amine; Ines Boufaied; Emmanuelle Lemyre; Pascal de Santa Barbara; Sandrine Faure; Anders Jonzon; Michel Cameron; Harry C. Dietz; Elena Gallo-McFarlane; D. Benson; Claudia Moreau; Damian Labuda; Shing H. Zhan; Yaoqing Shen; Michele Jomphe; Steven J. Jones; Jeroen Bakkers; Gregor Andelfinger

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

Translated title of the contribution: Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm

Philippe Chetaille, Christoph Preuss, S.B. Burkhard, Jean Marc Cote, Christine Houde, Julie Castilloux, Jessica Piche, Natacha Gosset, Severine Leclerc, Florian Wuennemann, Maryse Thibeault, Carmen Gagnon, Antonella Galli, Elizabeth Tuck, Gilles R. Hickson, Nour El Amine, Ines Boufaied, Emmanuelle Lemyre, Pascal de Santa Barbara, Sandrine FaureAnders Jonzon, Michel Cameron, Harry C. Dietz, Elena Gallo-McFarlane, D. Benson, Claudia Moreau, Damian Labuda, Shing H. Zhan, Yaoqing Shen, Michele Jomphe, Steven J. Jones, Jeroen Bakkers, Gregor Andelfinger

Research output: Contribution to journal › Article › Academic › peer-review

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-beta 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

Translated title of the contribution	Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
Original language	Undefined/Unknown
Pages (from-to)	1245-1249
Number of pages	5
Journal	Nature Genetics
Volume	46
Issue number	11
Publication status	Published - 2014

Cite this

Chetaille, P., Preuss, C., Burkhard, S. B., Marc Cote, J., Houde, C., Castilloux, J., Piche, J., Gosset, N., Leclerc, S., Wuennemann, F., Thibeault, M., Gagnon, C., Galli, A., Tuck, E., R. Hickson, G., El Amine, N., Boufaied, I., Lemyre, E., de Santa Barbara, P., ... Andelfinger, G. (2014). Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nature Genetics, 46(11), 1245-1249.

@article{1e35ae585dc1400f918fe9b281679c11,

title = "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-beta 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",

author = "Philippe Chetaille and Christoph Preuss and S.B. Burkhard and {Marc Cote}, Jean and Christine Houde and Julie Castilloux and Jessica Piche and Natacha Gosset and Severine Leclerc and Florian Wuennemann and Maryse Thibeault and Carmen Gagnon and Antonella Galli and Elizabeth Tuck and {R. Hickson}, Gilles and {El Amine}, Nour and Ines Boufaied and Emmanuelle Lemyre and {de Santa Barbara}, Pascal and Sandrine Faure and Anders Jonzon and Michel Cameron and {C. Dietz}, Harry and Elena Gallo-McFarlane and D. Benson and Claudia Moreau and Damian Labuda and {H. Zhan}, Shing and Yaoqing Shen and Michele Jomphe and {J. Jones}, Steven and Jeroen Bakkers and Gregor Andelfinger",

note = "J OV 2014",

year = "2014",

language = "Undefined/Unknown",

volume = "46",

pages = "1245--1249",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

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Chetaille, P, Preuss, C, Burkhard, SB, Marc Cote, J, Houde, C, Castilloux, J, Piche, J, Gosset, N, Leclerc, S, Wuennemann, F, Thibeault, M, Gagnon, C, Galli, A, Tuck, E, R. Hickson, G, El Amine, N, Boufaied, I, Lemyre, E, de Santa Barbara, P, Faure, S, Jonzon, A, Cameron, M, C. Dietz, H, Gallo-McFarlane, E, Benson, D, Moreau, C, Labuda, D, H. Zhan, S, Shen, Y, Jomphe, M, J. Jones, S, Bakkers, J & Andelfinger, G 2014, 'Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm', Nature Genetics, vol. 46, no. 11, pp. 1245-1249.

TY - JOUR

T1 - Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm

AU - Chetaille, Philippe

AU - Preuss, Christoph

AU - Burkhard, S.B.

AU - Marc Cote, Jean

AU - Houde, Christine

AU - Castilloux, Julie

AU - Piche, Jessica

AU - Gosset, Natacha

AU - Leclerc, Severine

AU - Wuennemann, Florian

AU - Thibeault, Maryse

AU - Gagnon, Carmen

AU - Galli, Antonella

AU - Tuck, Elizabeth

AU - R. Hickson, Gilles

AU - El Amine, Nour

AU - Boufaied, Ines

AU - Lemyre, Emmanuelle

AU - de Santa Barbara, Pascal

AU - Faure, Sandrine

AU - Jonzon, Anders

AU - Cameron, Michel

AU - C. Dietz, Harry

AU - Gallo-McFarlane, Elena

AU - Benson, D.

AU - Moreau, Claudia

AU - Labuda, Damian

AU - H. Zhan, Shing

AU - Shen, Yaoqing

AU - Jomphe, Michele

AU - J. Jones, Steven

AU - Bakkers, Jeroen

AU - Andelfinger, Gregor

N1 - J OV 2014

PY - 2014

Y1 - 2014

N2 - 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-beta 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

AB - 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-beta 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

M3 - Article

SN - 1061-4036

VL - 46

SP - 1245

EP - 1249

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

Abstract

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