title: Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds.
abstract: OBJECTIVE
  To assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, and DRPLA (dentatorubropallidoluysian atrophy) CAG trinucleotide repeat expansions [(CAG)n] among persons diagnosed with hereditary SCA from Chinese families.
  
  
  METHODS
  Spinocerebellar ataxia type 1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA (CAG)n mutation were detected with the polymerase chain reaction, highly denaturing polyacrylamide gel electrophoresis, and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 patients with sporadic SCA.
  
  
  RESULTS
  Spinocerebellar ataxia type 1 (CAG)n mutation in 7 patients from 4 kindreds (4.70%) was expanded to 53 to 62 repeats. Spinocerebellar ataxia type 2 (CAG)n mutation in 12 patients from 5 kindreds (5.88%) was expanded to 42 to 47 repeats. Spinocerebellar ataxia type 3/Machado-Joseph disease (CAG)n mutation in 83 patients from 41 kindreds (48.23%) was expanded to 68 to 83 repeats. Sixty-five patients from 35 kindreds (41.19%) and 37 patients with sporadic SCA did not test positive for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, or DRPLA. There was a predictable inverse relationship between the number of CAG repeats and the age at onset for SCA3/MJD and SCA2. Clinically, dementia and hyporeflexia were more frequent in patients with SCA2, while spasticity, hyperreflexia, and Babinski signs were more frequent in patients with SCA3/ MJD, and those might be helpful in clinical work to primarily distinguish patients with SCA3/MJD and SCA2 from others with different types of SCA.
  
  
  CONCLUSIONS
  The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in patients with autosomal dominant SCA from Chinese kindreds, who are non-Portuguese. Clinical expressions of the various types of SCAs overlap one another; therefore, for clinical study it is important to make a gene diagnosis and genetic classification for patients with SCA.
authors.affiliation: Department of Neurology, Xiangya Hospital, Hunan Medical University, People's Republic of China. neurogxm@public.cs.hn.cn
authors.forename: B
authors.initials: B
authors.lastname: Tang
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: H
authors.initials: H
authors.lastname: Dai
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.forename: L
authors.initials: L
authors.lastname: Jing
authors.forename: S
authors.initials: S
authors.lastname: Ouyang
authors.forename: J
authors.initials: J
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000067696:Ataxin-1; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015220:Calcium Channels / Q000235:genetics; D002648:Child; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012044:Regression Analysis; D012097:Repressor Proteins; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000453:epidemiology* / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D020864:Calcium Channels, N-Type
chemical_list: D000067696:Ataxin-1; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; C000593749:ATXN1 protein, human; C000593829:ATXN7 protein, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C095278:atrophin-1; C092341:ATXN3 protein, human