Candidate variants in TUB are associated with familial tremor

M. Reza Sailani, Fereshteh Jahanbani, Charles W. Abbott, Hayan Lee, Amin Zia, Shannon Rego, Juliane Winkelmann, Franziska Hopfner, Tahir N. Khan, Nicholas Katsanis, Stefanie H. Müller, Daniela Berg, Katherine M. Lyman, Christian Mychajliw, Günther Deuschl, Jonathan A. Bernstein, Gregor Kuhlenbäumer*, Michael P. Snyder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1009010
JournalPLoS genetics
Volume16
Issue number9
DOIs
StatePublished - Sep 2020

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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