@article{a4f8fd735f194b99add96b4a440828c0,
title = "Candidate variants in TUB are associated with familial tremor",
abstract = "Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p. V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.",
author = "{Reza Sailani}, M. and Fereshteh Jahanbani and Abbott, {Charles W.} and Hayan Lee and Amin Zia and Shannon Rego and Juliane Winkelmann and Franziska Hopfner and Khan, {Tahir N.} and Nicholas Katsanis and M{\"u}ller, {Stefanie H.} and Daniela Berg and Lyman, {Katherine M.} and Christian Mychajliw and G{\"u}nther Deuschl and Bernstein, {Jonathan A.} and Gregor Kuhlenb{\"a}umer and Snyder, {Michael P.}",
note = "Funding Information: This work was supported by the National Institutes of Health (www.nih.gov) and grant award NIH S10OD020141 to the SCGPM Genome Sequencing Service Center at Stanford. MRS was supported by grants P300PA_161005 and 551 P2GEP3_151825 from the Swiss National Science Foundation (SNSF) (http://www.snf.ch/en). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and SNSF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank all the patients and their families who participated in this study. We also thank Stanford Center for Genomics and Personalized Medicine (SCGPM) to provide the necessary computing and data storage resources. Publisher Copyright: {\textcopyright} 2020 Sailani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2020",
month = sep,
doi = "10.1371/journal.pgen.1009010",
language = "English (US)",
volume = "16",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "9",
}
