Title |
GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability
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Published in |
American Journal of Human Genetics, August 2016
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DOI | 10.1016/j.ajhg.2016.06.025 |
Pubmed ID | |
Authors |
Elisabeth M. Lodder, Pasquelena De Nittis, Charlotte D. Koopman, Wojciech Wiszniewski, Carolina Fischinger Moura de Souza, Najim Lahrouchi, Nicolas Guex, Valerio Napolioni, Federico Tessadori, Leander Beekman, Eline A. Nannenberg, Lamiae Boualla, Nico A. Blom, Wim de Graaff, Maarten Kamermans, Dario Cocciadiferro, Natascia Malerba, Barbara Mandriani, Zeynep Hande Coban Akdemir, Richard J. Fish, Mohammad K. Eldomery, Ilham Ratbi, Arthur A.M. Wilde, Teun de Boer, William F. Simonds, Marguerite Neerman-Arbez, V. Reid Sutton, Fernando Kok, James R. Lupski, Alexandre Reymond, Connie R. Bezzina, Jeroen Bakkers, Giuseppe Merla |
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. |
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Country | Count | As % |
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Switzerland | 4 | 29% |
United States | 3 | 21% |
Netherlands | 2 | 14% |
Greece | 1 | 7% |
Canada | 1 | 7% |
Unknown | 3 | 21% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 10 | 71% |
Scientists | 2 | 14% |
Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Mexico | 1 | 1% |
Unknown | 84 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 11 | 13% |
Student > Master | 10 | 12% |
Researcher | 9 | 11% |
Student > Ph. D. Student | 9 | 11% |
Student > Doctoral Student | 5 | 6% |
Other | 14 | 16% |
Unknown | 27 | 32% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 16 | 19% |
Medicine and Dentistry | 12 | 14% |
Agricultural and Biological Sciences | 10 | 12% |
Nursing and Health Professions | 6 | 7% |
Neuroscience | 6 | 7% |
Other | 1 | 1% |
Unknown | 34 | 40% |