TY - JOUR
T1 - Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the amish-mennonites
AU - Saunders-Pullman, Rachel
AU - Raymond, Deborah
AU - Senthil, Geetha
AU - Kramer, Patricia
AU - Ohmann, Erin
AU - Deligtisch, Amanda
AU - Shanker, Vicki
AU - Greene, Paul
AU - Tabamo, Rowena
AU - Huang, Neng
AU - Tagliati, Michele
AU - Kavanagh, Patricia
AU - Soto-Valencia, Jeannie
AU - Aguiar, Patricia de Carvalho
AU - Risch, Neil
AU - Ozelius, Laurie
AU - Bressman, Susan
PY - 2007/9/15
Y1 - 2007/9/15
N2 - 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.
AB - 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.
KW - Amish-Mennonite
KW - DYT6
KW - Dystonia
KW - Hereditary dystonia
KW - Primary
UR - http://www.scopus.com/inward/record.url?scp=38449113934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38449113934&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.31887
DO - 10.1002/ajmg.a.31887
M3 - Article
C2 - 17702011
AN - SCOPUS:38449113934
SN - 1552-4825
VL - 143
SP - 2098
EP - 2105
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 18
ER -