GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability.
Am J Hum Genet
; 99(3): 704-710, 2016 09 01.
Article
en En
| MEDLINE
| ID: mdl-27523599
ABSTRACT
GNB5 encodes the G protein ß subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal reflux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Nodo Sinoatrial
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Bradicardia
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Discapacidades del Desarrollo
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Subunidades beta de la Proteína de Unión al GTP
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Genes Recesivos
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Mutación
Límite:
Adolescent
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Adult
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Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Am J Hum Genet
Año:
2016
Tipo del documento:
Article
País de afiliación:
Países Bajos