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Title

GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability

Authors
Lodder, Elisabeth M
De Nittis, Pasquelena
Koopman, Charlotte D
Wiszniewski, Wojciech
Moura de Souza, Carolina Fischinger
Lahrouchi, Najim
Guex, Nicolas
Napolioni, Valerio
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Published in American Journal of Human Genetics. 2016
Abstract GNB5 encodes the G protein β 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.
Identifiers
PMID: 27523599
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Article (Preprint) (1.5 MB) - public document Free access
Structures
Research group Bases moléculaires des anomalies génétiques de l'hémostase (504)
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(ISO format)
LODDER, Elisabeth M et al. GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability. In: American Journal of Human Genetics, 2016. https://archive-ouverte.unige.ch/unige:86476

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Deposited on : 2016-08-30

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