| Literature DB >> 27523599 |
Elisabeth M Lodder1, Pasquelena De Nittis2, Charlotte D Koopman3, Wojciech Wiszniewski4, Carolina Fischinger Moura de Souza5, Najim Lahrouchi1, Nicolas Guex6, Valerio Napolioni7, Federico Tessadori8, Leander Beekman1, Eline A Nannenberg9, Lamiae Boualla10, Nico A Blom11, Wim de Graaff12, Maarten Kamermans13, Dario Cocciadiferro14, Natascia Malerba14, Barbara Mandriani15, Zeynep Hande Coban Akdemir4, Richard J Fish16, Mohammad K Eldomery4, Ilham Ratbi10, Arthur A M Wilde1, Teun de Boer17, William F Simonds18, Marguerite Neerman-Arbez16, V Reid Sutton19, Fernando Kok20, James R Lupski21, Alexandre Reymond22, Connie R Bezzina1, Jeroen Bakkers23, Giuseppe Merla24.
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.Entities:
Keywords: G-protein signaling; heart rate; hypotonia; intellectual disability; parasympathetic system; whole-exome sequencing
Mesh：
Substances：
Year: 2016 PMID： 27523599 PMCID： PMC5010642 DOI： 10.1016/j.ajhg.2016.06.025
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025