Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10

Raji P. Grewal, Madhureeta Achari, Tohru Matsuura, Alberto Durazo, Emilio Tayag, Lan Zu, Stefan M. Pulst, Tetsuo Ashizawa

Research output: Contribution to journalArticle

55 Scopus citations

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. Objectives: To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families. Design: Clinical characterization and genotypephenotype correlation. Setting: Studies at 2 medical schools with private practice referral. Patients: 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.

Original languageEnglish (US)
Pages (from-to)1285-1290
Number of pages6
JournalArchives of neurology
Volume59
Issue number8
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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