title: Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population.
abstract: OBJECTIVE
  Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies.
  
  
  METHODS
  Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location).
  
  
  RESULTS
  Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population.
  
  
  CONCLUSIONS
  Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Faruq
authors.affiliation: Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Achal Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Suman
authors.initials: S
authors.lastname: Singh
authors.forename: Rohit
authors.initials: R
authors.lastname: Gupta
authors.forename: Tanuj
authors.initials: T
authors.lastname: Dada
authors.forename: Ajay
authors.initials: A
authors.lastname: Garg
authors.forename: Madhuri
authors.initials: M
authors.lastname: Behari
authors.forename: Mitali
authors.initials: M
authors.lastname: Mukerji
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000067719:Ataxin-7 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7