Abstract
The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia‐dominated phenotypes. Massive gene analysis in next‐generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP‐based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.
Lingua originale | English |
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pagine (da-a) | 8490-N/A |
Rivista | International Journal of Molecular Sciences |
Volume | 22 |
DOI | |
Stato di pubblicazione | Pubblicato - 2021 |
Keywords
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Child
- Child, Preschool
- Cohort
- Diagnostic yield
- Exome sequencing
- Female
- Genesis
- Genetic Testing
- HA
- High-Throughput Nucleotide Sequencing
- Humans
- Male
- Middle Aged
- Mutation
- Next‐generation sequencing
- Spinocerebellar Degenerations
- TRP
- Targeted resequencing panel
- Variant
- Whole Exome Sequencing
- Young Adult