Spinocerebellar ataxia type 8

Molecular genetic comparisons and haplotype analysis of 37 families with ataxia

Yoshio Ikeda, Joline C. Dalton, Melinda L. Moseley, Kathy L. Gardner, Thomas D. Bird, Tetsuo Ashizawa, William K. Seltzer, Massimo Pandolfo, Aubrey Milunsky, Nicholas Potter, Mikio Shoji, John B. Vincent, John W. Day, Laura P.W. Ranum

Research output: Contribution to journalArticle

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Abstract

We reported elsewhere that an untranslated CTG expansion causes the dominantly inherited neurodegenerative disorder spinocerebellar ataxia type 8 (SCA8). SCA8 shows a complex inheritance pattern with extremes of incomplete penetrance, in which often only one or two affected individuals are found in a given family. SCA8 expansions have also been found in control chromosomes, indicating that separate genetic or environmental factors increase disease penetrance among SCA8-expansion-carrying patients with ataxia. We describe the molecular genetic features and disease penetrance of 37 different families with SCA8 ataxia from the United States, Canada, Japan, and Mexico. Haplotype analysis using 17 STR markers spanning an ∼1-Mb region was performed on the families with ataxia, on a group of expansion carriers in the general population, and on psychiatric patients, to clarify the genetic basis of the reduced penetrance and to investigate whether CTG expansions among different populations share a common ancestral background. Two major ancestrally related haplotypes (A and A′) were found among white families with ataxia, normal controls, and patients with major psychosis, indicating a common ancestral origin of both pathogenic and nonpathogenic SCA8 expansions among whites. Two additional and distinct haplotypes were found among a group of Japanese families with ataxia (haplotype B) and a Mexican family with ataxia (haplotype C). Our finding that SCA8 expansions on three independently arising haplotypes are found among patients with ataxia and cosegregate with ataxia when multiple family members are affected further supports the direct role of the CTG expansion in disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)3-16
Number of pages14
JournalAmerican Journal of Human Genetics
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2004

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Ataxia
Haplotypes
Molecular Biology
Penetrance
Inheritance Patterns
Inborn Genetic Diseases
Spinocerebellar ataxia 8
Mexico
Neurodegenerative Diseases
Psychotic Disorders
Population
Canada
Psychiatry
Japan
Chromosomes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Ikeda, Y., Dalton, J. C., Moseley, M. L., Gardner, K. L., Bird, T. D., Ashizawa, T., ... Ranum, L. P. W. (2004). Spinocerebellar ataxia type 8: Molecular genetic comparisons and haplotype analysis of 37 families with ataxia. American Journal of Human Genetics, 75(1), 3-16. https://doi.org/10.1086/422014

Spinocerebellar ataxia type 8 : Molecular genetic comparisons and haplotype analysis of 37 families with ataxia. / Ikeda, Yoshio; Dalton, Joline C.; Moseley, Melinda L.; Gardner, Kathy L.; Bird, Thomas D.; Ashizawa, Tetsuo; Seltzer, William K.; Pandolfo, Massimo; Milunsky, Aubrey; Potter, Nicholas; Shoji, Mikio; Vincent, John B.; Day, John W.; Ranum, Laura P.W.

In: American Journal of Human Genetics, Vol. 75, No. 1, 01.01.2004, p. 3-16.

Research output: Contribution to journalArticle

Ikeda, Y, Dalton, JC, Moseley, ML, Gardner, KL, Bird, TD, Ashizawa, T, Seltzer, WK, Pandolfo, M, Milunsky, A, Potter, N, Shoji, M, Vincent, JB, Day, JW & Ranum, LPW 2004, 'Spinocerebellar ataxia type 8: Molecular genetic comparisons and haplotype analysis of 37 families with ataxia', American Journal of Human Genetics, vol. 75, no. 1, pp. 3-16. https://doi.org/10.1086/422014
Ikeda, Yoshio ; Dalton, Joline C. ; Moseley, Melinda L. ; Gardner, Kathy L. ; Bird, Thomas D. ; Ashizawa, Tetsuo ; Seltzer, William K. ; Pandolfo, Massimo ; Milunsky, Aubrey ; Potter, Nicholas ; Shoji, Mikio ; Vincent, John B. ; Day, John W. ; Ranum, Laura P.W. / Spinocerebellar ataxia type 8 : Molecular genetic comparisons and haplotype analysis of 37 families with ataxia. In: American Journal of Human Genetics. 2004 ; Vol. 75, No. 1. pp. 3-16.
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