title: Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10.
abstract: BACKGROUND
  Spinocerebellar ataxia type 10, an autosomal dominant disease characterized by ataxia and seizures, is caused by a large expansion of an unstable ATTCT pentanucleotide repeat.
  
  
  OBJECTIVE
  To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families.
  
  
  METHODS
  Clinical characterization and genotype-phenotype correlation.
  
  
  METHODS
  Studies at 2 medical schools with private practice referral.
  
  
  METHODS
  Twenty-two affected individuals from 2 large Mexican American pedigrees.
  
  
  RESULTS
  Of the 22 individuals, ataxia was the initial symptom in 21; seizure disorders developed in 11, mostly within several years following the onset of ataxia. The seizure frequency was different in the 2 families: 3 (25%) of 12 had seizures in family 1, and 8 (80%) of 10 had seizures in family 2 (P =.01). A brain magnetic resonance imaging or computed tomographic scan showed cerebellar atrophy in all patients examined. An electroencephalogram demonstrated epileptiform discharges in 4 of 8 patients studied. Although anticipation was apparent in both families, only family 1 showed a strong inverse correlation between age of onset and repeat number (r(2) = 0.79, P =.001). In family 1, 8 transmissions, of which 7 were paternal, resulted in an average gain of 1940 repeats. In contrast, despite anticipation, 2 affected male subjects transmitted their expanded alleles to 8 progenies, with an average loss of 755 repeats, in family 2.
  
  
  CONCLUSIONS
  Seizure is an integral part of the spinocerebellar ataxia type 10 phenotype, with documented morbidity and mortality. Family-dependent factors may alter the frequency of the seizure phenotype and the pattern of intergenerational repeat size changes, making the genotype-phenotype correlation complex.
authors.affiliation: New Jersey Neuroscience Institute, Seton Hall University, Edison, NJ, USA.
authors.forename: Raji P
authors.initials: RP
authors.lastname: Grewal
authors.forename: Madhureeta
authors.initials: M
authors.lastname: Achari
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Alberto
authors.initials: A
authors.lastname: Durazo
authors.forename: Emilio
authors.initials: E
authors.lastname: Tayag
authors.forename: Lan
authors.initials: L
authors.lastname: Zu
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pulst
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
mesh_terms: D000328:Adult; D002648:Child; D017029:Epilepsy, Complex Partial / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012091:Repetitive Sequences, Nucleic Acid; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology