title: Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases.
abstract: OBJECTIVE
  To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China.
  
  
  METHODS
  SCA 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA) and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently, point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13, SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and DNA direct sequencing analysis.
  
  
  RESULTS
  Among the 430 ADCA families, there were 25 SCA1 (5.81%), 27 SCA2 (6.28%), 267 SCA3/MJD (62.09%), 8 SCA6 (1.86%), 8 SCA7 (1.86%), 1 SCA12 (0.23%), 1 SCA17 (0.23%) and 2 SCA35 (0.47%), and the remaining 91 families (21.16%) were genetically unidentified. Among the 237 sporadic SCA patients, there were 6 SCA1 (2.53%), 9 SCA2 (3.80%), 23 SCA3/MJD (9.70%) and 3 SCA6 (1.27%), and the remaining 196 (82.7%) were genetically unidentified. No pathogenic point mutation causing SCA5, SCA11, SCA13, SCA14, SCA27 or SCA31 subtypes was found.
  
  
  CONCLUSIONS
  SCA3/MJD is substantially the most common subtype in patients with ADCA and sporadic forms in mainland China, followed by SCA2, SCA1, SCA6 and SCA7. While SCA12, SCA17 and SCA35 are seldom found, SCA5, SCA8, SCA10, SCA11, SCA13, SCA27, SCA31 and DRPLA are very rare. The high proportion of genetically unidentified cases further verify that SCAs are of highly genetic heterogeneity, suggesting that other disease-causing genes might be involved in the negative ADCA pedigrees, and other etiological factors may involve in those sporadic cases other than genetics.
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Junling
authors: J
authors: Wang
authors: Lu
authors: L
authors: Shen
authors: Lifang
authors: L
authors: Lei
authors: Qian
authors: Q
authors: Xu
authors: Jie
authors: J
authors: Zhou
authors: Yutao
authors: Y
authors: Liu
authors: Wenjuan
authors: W
authors: Guan
authors: Qian
authors: Q
authors: Pan
authors: Kun
authors: K
authors: Xia
authors: Beisha
authors: B
authors: Tang
authors: Hong
authors: H
authors: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D000067696:Ataxin-1; D000067699:Ataxin-3; D000067528:Ataxins; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3