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Scientific article
English

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

Published inAmerican journal of human genetics, vol. 99, no. 3, p. 704-710
Publication date2016
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.

Citation (ISO format)
LODDER, Elisabeth M, DE NITTIS, Pasquelena, KOOPMAN, Charlotte D. GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability. In: American journal of human genetics, 2016, vol. 99, n° 3, p. 704–710. doi: 10.1016/j.ajhg.2016.06.025
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ISSN of the journal0002-9297
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Creation08/24/2016 8:41:00 AM
First validation08/24/2016 8:41:00 AM
Update time03/15/2023 12:40:50 AM
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