Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the amish-mennonites

Rachel Saunders-Pullman, Deborah Raymond, Geetha Senthil, Patricia Kramer, Erin Ohmann, Amanda Deligtisch, Vicki Shanker, Paul Greene, Rowena Tabamo, Neng Huang, Michele Tagliati, Patricia Kavanagh, Jeannie Soto-Valencia, Patricia de Carvalho Aguiar, Neil Risch, Laurie Ozelius, Susan Bressman

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The DYT6 gene for primary torsion dystonia (PTD) was mapped to chromosome 8p21-q22 in two Amish-Mennonite families who shared a haplotype of marker alleles across a 40 cM linked region. The objective of this study was to narrow the DYT6 region, clinically characterize DYT6 dystonia in a larger cohort, and to determine whether DYT6 is associated with dystonia in newly ascertained multiplex families. We systematically examined familial Amish-Mennonite dystonia cases, identifying five additional members from the original families, as well as three other multiplex Amish-Mennonite families, and evaluated the known DYT6 haplotype and recombination events. One of the three new families carried the shared haplotype, whereas the region was excluded in the two other families, suggesting genetic heterogeneity for PTD in the Amish-Mennonites. Clinical features in the five newly identified DYT6 carriers were similar to those initially described. In contrast, affected individuals from the excluded families had a later age of onset (46.9 years vs. 16.1 years in the DYT6), and the dystonia was both more likely to be of focal distribution and begin in the cervical muscles. Typing of additional markers in the DYT6-linked families revealed recombinations that now place the gene in a 23 cM region surrounding the centromere. In summary, the DYT6 gene is in a 23 cM region on chromosome 8q21-22 and does not account for all familial PTD in Amish-Mennonites.

Original languageEnglish (US)
Pages (from-to)2098-2105
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume143
Issue number18
DOIs
StatePublished - Sep 15 2007

Keywords

  • Amish-Mennonite
  • DYT6
  • Dystonia
  • Hereditary dystonia
  • Primary

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Saunders-Pullman, R., Raymond, D., Senthil, G., Kramer, P., Ohmann, E., Deligtisch, A., Shanker, V., Greene, P., Tabamo, R., Huang, N., Tagliati, M., Kavanagh, P., Soto-Valencia, J., Aguiar, P. D. C., Risch, N., Ozelius, L., & Bressman, S. (2007). Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the amish-mennonites. American Journal of Medical Genetics, Part A, 143(18), 2098-2105. https://doi.org/10.1002/ajmg.a.31887