Clinical diagnostic exome sequencing in dystonia: Genetic testing challenges for complex conditions.
Clin Genet
; 97(2): 305-311, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31628766
ABSTRACT
Patients with dystonia are particularly appropriate for diagnostic exome sequencing (DES), due to the complex, diverse features and genetic heterogeneity. Personal and family history data were collected from test requisition forms and medical records from 189 patients with reported dystonia and available family members received for clinical DES. Of them, 20.2% patients had a positive genetic finding associated with dystonia. Detection rates for cases with isolated and combined dystonia were 22.4% and 25.0%, respectively. 71.4% of the cohort had co-occurring non-movement-related findings and a detection rate of 24.4%. Patients with childhood-onset dystonia trended toward higher detection rates (31.8%) compared to infancy (23.6%), adolescence (12.5%), and early-adulthood onset (16%). Uncharacterized gene findings were found in 6.7% (8/119) of cases that underwent analysis for genes without an established disease relationship. Patients with intellectual disability/developmental delay, seizures/epilepsy and/or multifocal dystonia were more likely to have positive findings (P = .0093, .0397, .0006). Four (2.1%) patients had findings in two genes, and seven (3.7%) had reclassification after the original report due to new literature, new clinical information or reanalysis request. Pediatric patients were more likely to have positive findings (P = .0180). Our observations show utility of family-based DES in patients with dystonia and illustrate the complexity of testing.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenylyl Cyclases
/
Dystonic Disorders
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Dystonia
/
Intellectual Disability
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
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Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Clin Genet
Year:
2020
Document type:
Article