Journal article
Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy
Egidio Spinelli, Kyle R Christensen, Emily Bryant, Amy Schneider, Jennifer Rakotomamonjy, Alison M Muir, Jessica Giannelli, Rebecca O Littlejohn, Elizabeth R Roeder, Berkley Schmidt, William G Wilson, Elysa J Marco, Kazuhiro Iwama, Satoko Kumada, Tiziana Pisano, Carmen Barba, Annalisa Vetro, Eva H Brilstra, Richard H Jaarsveld, Naomichi Matsumoto Show all
ANNALS OF NEUROLOGY | WILEY | Published : 2021
DOI: 10.1002/ana.26147
Abstract
OBJECTIVE: The MAST family of microtubule-associated serine-threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum. METHODS: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells. RESULTS: We identify de novo missense variants in the STK domain in 11 individuals, including 2 recurrent va..
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Awarded by NIH NINDS
Awarded by Japan Agency for Medical Research and Development (AMED)
Awarded by JSPS KAKENHI
Awarded by NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH
Funding Acknowledgements
We would like to thank the patients and families for their participation in this research study. This work was sponsored by NIH NINDS R00NS089858 (G.L.C.), National Health and Medical Research Council of Australia, CURE, Australian Epilepsy Research Fund, March of Dimes and NIH/NINDS (I.E.S.), the Japan Agency for Medical Research and Development (AMED) under grant numbers JP20ek0109280, JP20dm0107090, JP20ek0109301, JP20ek0109348, and JP20kk0205012 (N.M.), JSPS KAKENHI under grant numbers JP17H01539 (N.M.), JP20K16862 (K.I.); a pilot award from the Swebilius Foundation at Yale University (A.C.N.), NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under Award Numbers U01HG007690 and U01HG007530 (L.H.R., The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), K.M.C. is an employee of GeneDx, Inc. Research reported in this manuscript was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under Award Numbers U01HG007690 and U01HG007530. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Undiagnosed Diseases Network (UDN) members: .