Candidate variants in TUB are associated with familial tremor

Autoři: M. Reza Sailani aff001;  Fereshteh Jahanbani aff001;  Charles W. Abbott aff001;  Hayan Lee aff001;  Amin Zia aff001;  Shannon Rego aff001;  Juliane Winkelmann aff002;  Franziska Hopfner aff003;  Tahir N. Khan aff005;  Nicholas Katsanis aff005;  Stefanie H. Müller aff003;  Daniela Berg aff003;  Katherine M. Lyman aff001;  Christian Mychajliw aff009;  Günther Deuschl aff003;  Jonathan A. Bernstein aff010;  Gregor Kuhlenbäumer aff003;  Michael P. Snyder aff001
Působiště autorů: Department of Genetics, Stanford University, Stanford, CA, United States of America aff001;  Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany; Institute of Human Genetics, Technical University, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany aff002;  Department of Neurology, Kiel University, Germany aff003;  Department of Neurology, Hannover Medical School, Hannover, Germany aff004;  Center for Human Disease Modeling, Duke University, United States of America aff005;  Advanced Center for Translational and Genetic Medicine, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, United States of America aff006;  Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America aff007;  Department of Neurology, Universitätsklinikum Tübingen, Germany aff008;  University Hospital Tübingen, Department of Psychiatry and Psychotherapy, Tübingen, Germany aff009;  Department of Pediatrics, Stanford University, Stanford, CA, United States of America aff010
Vyšlo v časopise: Candidate variants in TUB are associated with familial tremor. PLoS Genet 16(9): e32767. doi:10.1371/journal.pgen.1009010
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009010


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.

Klíčová slova:

Cerebellum – Hormone receptor signaling – Mammalian genomics – Neostriatum – Polymerase chain reaction – Thyroid hormones – Transcription factors – Myoclonus


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