Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect
Romanelli Tavares, Vanessa L.
Gordon, Christopher T.
Zechi-Ceide, Roseli M.
Kokitsu-Nakata, Nancy Mizue
Tan, Tiong Y.
Heggie, Andrew A.
Propst, Evan J.
Papsin, Blake C.
Torres, Tatiana T.
Capelo, Luciane Portas [UNIFESP]
den Dunnen, Johan T.
Guion-Almeida, Maria L.
Passos-Bueno, Maria Rita
Is part ofEuropean Journal of Human Genetics
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Auriculocondylar syndrome is a rare craniofacial disorder comprising core features of micrognathia, condyle dysplasia and question mark ear. Causative variants have been identified in PLCB4, GNAI3 and EDN1, which are predicted to function within the EDN1-EDNRA pathway during early pharyngeal arch patterning. To date, two GNAI3 variants in three families have been reported. Here we report three novel GNAI3 variants, one segregating with affected members in a family previously linked to 1p21.1-q23.3 and two de novo variants in simplex cases. Two variants occur in known functional motifs, the G1 and G4 boxes, and the third variant is one amino acid outside of the G1 box. Structural modeling shows that all five altered GNAI3 residues identified to date cluster in a region involved in GDP/GTP binding. We hypothesize that all GNAI3 variants lead to dominant negative effects.
CitationEuropean Journal of Human Genetics. London: Nature Publishing Group, v. 23, n. 4, p. 481-485, 2015.
Universite Paris Descartes-Sorbonne Paris Cite Pole de Recherche et d'Enseignement Superieur
Agence Nationale de la Recherche (project EvoDevoMut)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
National Health and Medical Research Council of Australia
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