Document Type : Original Research Article

10.22034/HBB.2020.15

Abstract

This study aimed at assessing the methylation state of the DYT1 gene in the pathogenesis of dystonia disease and evaluated the clinical feature. Thirty patients with no mutation in DYT1 gene and 30 normal individuals were investigated. The methylation of promoter in DYT1 gene was investigated using Real-time PCR technique. There was no significant difference in methylation status of DYT1 gene promoter in the dystonia patients compared with normal individuals, showed that the methylation of promoter in DYT1 gene had no important role in dystonia. Also, the methylation of promoter in DYT1 gene was observed with higher frequency in the generalized type, suggesting that the methylation of this gene may play a role in pathogenesis of this type of dystonia.

Keywords

[1]. Charlesworth G, Bhatia KP, Wood NW. The genetics of dystonia: new twists in an old tale. Brain. 2013; 136(7): 2017-37.
[2]. Fahn S. Concept and classification of dystonia. Adv Neurol.1988, 50, 1.
[3]. Broussolle E, Laurencin C, Bernard E, Thobois S, Danaila T, Krack P. Early illustrations of geste antagoniste in cervical and generalized dystonia. Tremor Other Hyperkinet Mov. 2015; 5.
[4]. Wichmann T. Commentary: Dopaminergic dysfunction in DYT1 dystonia. Exp Neurol. 2008; 212(2): 242-46.
[5]. Kamm C. Early onset torsion dystonia (Oppenheim's dystonia). Orphanet J Rare Dis. 2006;1(1): 1-6.
[6]. Camargo CHF, Camargos ST, Cardoso FEC, Teive HAG. The genetics of the dystonias–a review based on the new classification of the dystonias. Arq Neuropsiquiatr. 2015; 73(4): 350-58.
[7]. Chuang C, Fahn S, Frucht S. The natural history and treatment of acquired hemidystonia: report of 33 cases and review of the literature. J Neurol Neurosurg Psychiatry. 2002;72(1): 59-67.
[8]. Tarsy D, Simon DK. Dystonia. N Engl J Med. 2006; 355(8): 818-29.
[9]. Albanese A, Bhatia K, Bressman SB, DeLong MR, Fahn S, Fung VS, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013; 28(7): 863-73.
[10]. Bressman SB, De Leon D, Brin MF, Risch N, Burke RE, Greene PE, et al. Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann Neurol. 1989; 26(5): 612-20.
[11]. Geyer HL, Bressman SB. The diagnosis of dystonia. Lancet Neurol. 2006; 5(9): 780-90.
[12]. O’riordan S, Raymond D, Lynch T, Saunders-Pullman R, Bressman S, Daly L, et al. Age at onset as a factor in determining the phenotype of primary torsion dystonia. Neurology. 2004; 63(8): 1423-26.
[13]. Jamora R, Tan A, Tan L. A 9‐year review of dystonia from a movement disorders clinic in Singapore. Eur J Neurol. 2006; 13(1): 77-81.
[14]. Del Sorbo F, Albanese A. Dystonia, In: Movement Disorders Curricula. 2017; 253-63.
[15]. Zorzi G, Zibordi F, Garavaglia B, Nardocci N. Early onset primary dystonia. Eur J Paediatr Neurol. 2009; 13(6): 488-92.
[16]. Leung J, Klein C, Friedman J, Vieregge P, Jacobs H, Doheny D, et al. Novel mutation in the TOR1A (DYT1) gene in atypical, early onset dystonia and polymorphisms in dystonia and early onset parkinsonism. Neurogenetics. 200; 3(3): 133-43.
[17]. Albanese A. Dystonia: clinical approach. Parkinsonism Relat Disord. 2007; 13, 356-61.
[18]. Kramer P, Heiman G, Gasser T, Ozelius L, De Leon D, Brin M, Burke R. The DYT1 gene on 9q34 is responsible for most cases of early limb-onset idiopathic torsion dystonia in non-Jews. Am J Hum Genet. 1994; 55(3): 468.
[19]. Hamid M, Akbari MT, Shahidi GA, Zand Z. The frequency of DYT1 (GAG Deletion) mutation in primary dystonia patients from Iran. Cell J. 2011; 13(1): 55.
[20]. MWer S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids Res. 1988; 16(3): 1215.
[21]. Rahnavard S, Hamid M, Zand Z. Investigating kinship in primary Dystonia patients without mutation in DYT1 gene in Iran. IOAB J. 2016; 7: 291-94.
[22]. Hamamy H. Consanguineous marriages. J Community Genet. 2012; 3(3): 185-92.
[23]. Saadat M, Ansari-Lari M, Farhud D. Short report consanguineous marriage in Iran. Ann Hum Biol.2004; 31(2), 263-69.