Open AccessCandidate variants in TUB are associated with familial tremor
Author(s) -
M. Reza Sailani,
Fereshteh Jahanbani,
Charles W. Abbott,
Hayan Lee,
Amin Zia,
Shan Rego,
Juliane Winkelmann,
Franziska Hopfner,
Tahir Naeem Khan,
Nicholas Katsanis,
Stefanie H. Müller,
Daniela Berg,
Katherine M. Lyman,
Christian Mychajliw,
Günther Deuschl,
Jonathan A. Bernstein,
Gregor Kuhlenbäumer,
M Snyder
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009010
Subject(s) - biology , exome sequencing , genetics , transcription factor , nonsynonymous substitution , essential tremor , exome , gene , mutation , neuroscience , genome
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.