DOI: 10.3724/SP.J.1206.2010.00083

Progress in Biochemistry and Biophysics (生物化学与生物物理进展) 2011/38:1 PP.5-10

Progress in Genetics of Essential Tremor*

Essential tremor is one of the most common neurological disorders which the causes remain unknown. The clinical feature is heterogeneous and many ET patients have positive family history. Thus far, three gene loci have been identified and two susceptibility genes including DRD3 (the dopamine receptor D3 gene) and LINGO1 (the Leucine-rich repeat-and lg domain-containing NOGO receptor-interacting protein 1 gene) have been reported recently. The genetics of essential tremor will be summarized.

Key words:essential tremor, susceptibility gene, DRD3, LINGO1, animal models

ReleaseDate:2014-07-21 15:46:45

Funds:This work was supported by grants from The National Natural Science Foundation of China(30871351, 30971534), Trans-Century Training Program Foundation for the Talents by The State Education Commission (NCET-080563), The Fund for Distinguished Young Scholar of Hunan Province (09JJ1005), The Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (H.D.), Sheng Hua Scholars Program and Outstanding Youth Foundation of Central South University, China (H.D.) and Aid program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province

[1] Deng H, Le W, Jankovic J. Genetics of essential tremor. Brain, 2007, 130(Pt 6): 1456-1464

[2] Deuschl G, Elble R. Essential tremor-neurodegenerative or nondegenerative disease towards a working definition of ET. Mov Disord, 2009, 24(14): 2033-2041

[3] Louis E D, Vonsattel J P, Honig L S, et al. Essential tremor associated with pathologic changes in the cerebellum. Arch Neurol, 2006, 63(8): 1189-1193

[4] Louis E D, Benito-León J, Bermejo-Pareja F. Population-based study of baseline ethanol consumption and risk of incident essential tremor. J Neurol Neurosurg Psychiatry, 2009, 80(5): 494-497

[5] Louis E D, Erickson-Davis C, Pahwa R, et al. Essential tremor with ubiquitinated Purkinje cell intranuclear inclusions. Acta Neuropathol, 2010, 119(3): 375-377

[6] Louis E D, Applegate L M, Rios E. ICD-9 CM code 333.1 as an identifier of patients with essential tremor: a study of the positive predictive value of this code. Neuroepidemiology, 2007, 28(3): 181-185

[7] Benito-León J. How common is essential tremor?. Neuroepidemiology, 2009, 32(3): 215-216

[8] Ferrara J, Jankovic J. Epidemiology and management of essential tremor in children. P aediatr Drugs, 2009, 11(5): 293-307

[9] Louis E D, Ottman R. Study of possible factors associated with age of onset in essential tremor. Mov Disord, 2006, 21(11): 1980-1986

[10] Lorenz D, Frederiksen H, Moises H, et al. High concordance for essential tremor in monozygotic twins of old age. Neurology, 2004, 62(2): 208-211

[11] Tanner C M, Goldman S M, Lyons K E, et al. Essential tremor in twins: an assessment of genetic vs environmental determinants of etiology. Neurology, 2001, 57(8): 1389-1391

[12] Louis E D. Etiology of essential tremor: should we be searching for environmental causes?. Mov Disord, 2001, 16(5): 822-829

[13] Ma S, Davis T L, Blair M A, et al. Familial essential tremor with apparent autosomal dominant inheritance: should we also consider other inheritance modes?. Mov Disord, 2006, 21(9): 1368-1374

[14] Gulcher J R, Jonsson P, Kong A, et al. Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nature Genet, 1997, 17(1): 84-87

[15] Jeanneteau F, Funalot B, Jankovic J, et al. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Nat Acad Sci USA, 2006, 103(28): 10753- 10758

[16] Lorenz D, Klebe S, Stevanin G, et al. Dopamine receptor D3 gene and essential tremor in large series of German, Danish and French patients. Eur J Hum Genet, 2009, 17(6): 766-773

[17] García-Martín E, Martínez C, Alonso-Navarro H, et al. Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor. Mov Disord, 2009, 24(13): 1910-1915

[18] Higgins J J, Pho L T, Nee L E. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov Disord, 1997, 12(6): 859-864

[19] Higgins J J, Jankovic J, Lombardi R Q, et al. Haplotype analysis of the ETM2 locus in familial essential tremor. Neurogenetics, 2003, 4(4): 185-189

[20] Kim J H, Cho Y H, Kim J K, et al. Frequent sequence variation at the ETM2 locus and its association with sporadic essential tremor in Korea. Mov Disord, 2005, 20(12): 1650-1653

[21] Higgins J J, Lombardi R Q, Pucilowska J, et al. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology, 2005, 64(3): 417-421

[22] Deng H, Le W D, Guo Y, et al. Extended study of A265G variant of HS1BP3 in essential tremor and Parkinson disease. Neurology, 2005, 65(4): 651-652

[23] Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain, 2006, 129(Pt 9): 2318-2331

[24] Carim-Todd L, Escarceller M, Estivill X, et al. LRRN6A/LERN1(leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex. Europ J Neurosci, 2003, 18(12): 3167-3182

[25] Pigullo S, Di Maria E, Marchese R, et al. Essential tremor is not associated with alpha-synuclein gene haplotypes. Mov Disord, 2003, 18(7): 823-826

[26] Ledesma M C, García-Martín E, Alonso-Navarro H, et al. The nonsynonymous Thr105Ile polymorphism of the histamine N-methyltransferase is associated to the risk of developing essential tremor. Neuromolecular Med, 2008, 10(4): 356-361

[27] Illarioshkin S N, Rakhmonov R A, Ivanova-Smolenskaia I A, et al. Molecular genetic analysis of essential tremor. Genetika, 2002, 38(12): 1704-1709

[28] Kaneko K, Igarashi S, Miyatake T, et al. Essential tremor and CAG repeats in the androgen receptor gene. Neurology, 1993, 43(8): 1618-1619

[29] Nicoletti G, Annesi G, Carrideo S, et al. Familial essential tremor is not associated with SCA-12 mutation in southern Italy. Mov Disord, 2002, 17(4): 837-838

[30] Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet, 2009, 41(3):277-279

[31] Carim-Todd L, Escarceller M, Estivill X, et al. LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex. Europ J Neurosci, 2003, 18(12): 3167-3182

[32] Mi S, Miller R H, Lee X, et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nature Neurosci, 2005, 8(6): 745-751

[33] Inoue H, Lin L, Lee X, et al. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Nat Acad Sci USA, 2007, 104(36): 14430-14435

[34] Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord, 2010, 25(6):709-715

[35] Tan E K, Teo Y Y, Prakash K M, et al. LINGO1 variant increases risk of familial essential tremor. Neurology, 2009, 73(14): 1161- 1162

[36] Clark L N, Park N, Kisselev S, et al. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet, 2010, 18(7): 838-843

[37] Vilarino-Güell C, Wider C, Ross O A, et al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics, 2010, 11(4): 401-408

[38] Miwa H. Rodent models of tremor. Cerebellum, 2007, 6(1): 66-72

[39] Kralic J E, Criswell H E, Osterman J L, et al. Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice. J Clin Invest, 2005, 115(3): 774-779

[40] Deng H, Xie W J, Le W D, et al. Genetic analysis of the GABRA1 gene in patients with essential tremor. Neurosci Lett, 2006, 401(1-2): 16-19

[41] Sharkey L M, Jones J M, Hedera P, et al. Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor. Parkinsonism Relat Disord, 2009, 15(4): 321-323