Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.
Nat Genet
; 46(11): 1245-9, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25282101
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-ß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
/
Anomalías Múltiples
/
Proteínas Cromosómicas no Histona
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Transducción de Señal
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Proteínas de Ciclo Celular
/
Enfermedades Intestinales
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Contracción Muscular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Canadá