Intragenic Cis and Trans modification of genetic susceptibility in DYT1 torsion dystonia.
Am J Hum Genet
; 80(6): 1188-93, 2007 Jun.
Article
en En
| MEDLINE
| ID: mdl-17503336
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Chaperonas Moleculares
/
Predisposición Genética a la Enfermedad
/
ADN Intergénico
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Distonía Muscular Deformante
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos