Genetic spectrum and clinical features in a cohort of Chinese patients with isolated dystonia.
Clin Genet
; 103(4): 459-465, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36648081
ABSTRACT
Dystonia is a genetically and phenotypically heterogeneous disorder that occurs in isolation (isolated dystonia) or in combination with other movement disorders. To determine the genetic spectrum in isolated dystonia, we enrolled 88 patients with isolated dystonia for whole-exome sequencing (WES). Seventeen mutations, including nine novel ones, were identified in 19 of the 88 patients, providing a 21.59% positive molecular diagnostic rate. Eleven distinct genes were involved, of which TOR1A and THAP1 accounted for 47.37% (9/19) of the positive cases. A novel missense variant, p.S225R in TOR1A, was found in a patient with adolescence-onset generalized dystonia. Cellular experiments revealed that p.S255R results in the abnormal aggregation of Torsin-1A encoding by TOR1A. In addition, we reviewed the clinical and genetic features of the isolated dystonia patients carrying TOR1A, THAP1, ANO3, and GNAL mutations in the Chinese population. Our results expand the genetic spectrum and clinical profiles of patients with isolated dystonia and demonstrate WES as an effective strategy for the molecular diagnosis of isolated dystonia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos Distónicos
/
Distonía
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Genet
Año:
2023
Tipo del documento:
Article
País de afiliación:
China