کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2812227 | 1569297 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Intragenic Cis and Trans Modification of Genetic Susceptibility in DYT1 Torsion Dystonia Intragenic Cis and Trans Modification of Genetic Susceptibility in DYT1 Torsion Dystonia](/preview/png/2812227.png)
A GAG deletion in the DYT1 gene is a major cause of early-onset dystonia, but clinical disease expression occurs in only 30% of mutation carriers. To gain insight into genetic factors that may influence penetrance, we evaluated three DYT1 single-nucleotide polymorphisms, including D216H, a coding-sequence variation that moderates the effects of the DYT1 GAG deletion in cellular models. We tested DYT1 GAG-deletion carriers with (n=119) and without (n=113) clinical signs of dystonia and control individuals (n=197) and found the frequency of the 216H allele to be increased in GAG-deletion carriers without dystonia and to be decreased in carriers with dystonia, compared with the control individuals. Analysis of haplotypes demonstrated a highly protective effect of the H allele in trans with the GAG deletion; there was also suggestive evidence that the D216 allele in cis is required for the disease to be penetrant. Our findings establish, for the first time, a clinically relevant gene modifier of DYT1.
Journal: - Volume 80, Issue 6, June 2007, Pages 1188–1193