The spinocerebellar ataxias: order emerges from chaos.

被引:49
作者
Margolis R.L. [1 ]
机构
[1] Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, 21287, MD
基金
美国国家卫生研究院;
关键词
Cerebellar Ataxia; Polyglutamine; Repeat Length; Repeat Expansion; Spinocerebellar Ataxia;
D O I
10.1007/s11910-002-0072-8
中图分类号
学科分类号
摘要
In the past decade, the genetic etiologies accounting for most cases of adult-onset dominant cerebellar ataxia have been discovered. This group of disorders, generally referred to as the spinocerebellar ataxias (SCAs), can now be classified by a simple genetic nosology, essentially a sequential list in which each new SCA is given a number. However, recent advances in the elucidation of SCA pathogenesis provide the opportunity to subclassify the disorders into three discrete groups based on pathogenesis: 1) the polyglutamine disorders, SCAs 1, 2, 3, 7, and 17, which result from proteins with toxic stretches of polyglutamine; 2) the channelopathies, SCA6 and episodic ataxia types 1 and 2 (EA1 and EA2), which result from disruption of calcium or potassium channel function; and 3) the gene expression disorders, SCAs 8, 10, and 12, which result from repeat expansions outside of coding regions that may quantitatively alter gene expression. SCAs 4, 5, 9, 11, 13-16, 19, 21, and 22 are of unknown etiology, and may or may not fit into one of these three groups. At present, most diagnostic and therapeutic strategies apply equally to all of the SCAs. Therapy specific for individual diseases or types of diseases is a realistic goal in the foreseeable future.
引用
收藏
页码:447 / 456
页数:9
相关论文
共 232 条
  • [1] van de Warrenburg BP(2001)Autosomal dominant cerebellar ataxias in the Netherlands: a national inventory Ned Tijdschr Geneeskd 145 962-967
  • [2] Silva MC(1997)Hereditary ataxias and spastic paraplegias: methodological aspects of a prevalence study in Portugal J Clin Epidemiol 50 1377-1384
  • [3] Coutinho P(1995)Structural and immunocytochemical features of olivopontocerebellar atrophy caused by the spinocerebellar ataxia type 1 (SCA-1) mutation define a unique phenotype Acta Neuropathol (Berl) 90 572-581
  • [4] Pinheiro CD(1997)The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia Am J Hum Genet 60 842-850
  • [5] Robitaille Y(1997)Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families Hum Mol Genet 6 709-715
  • [6] Schut L(1999)Spinocerebellar ataxia 2 (SCA2): morphometric analyses in 11 autopsies Acta Neuropathol (Berl) 97 306-310
  • [7] Kish SJ(1998)Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7) Hum Mol Genet 7 165-170
  • [8] Geschwind DH(1994)On an autosomal dominant form of retinal-cerebellar degeneration: an autopsy study of five patients in one family Acta Neuropathol (Berl) 88 277-286
  • [9] Perlman S(2001)SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein Hum Mol Genet 10 1441-1448
  • [10] Figueroa CP(2001)Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia Eur J Hum Genet 9 160-164