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.

Ngs in hereditary ataxia: When rare becomes frequent

Battini R.;
2021-01-01

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.
2021
Galatolo, D.; De Michele, G.; Silvestri, G.; Leuzzi, V.; Casali, C.; Musumeci, O.; Antenora, A.; Astrea, G.; Barghigiani, M.; Battini, R.; Battisti, C.; Caputi, C.; Cioffi, E.; De Michele, G.; Dotti, M. T.; Fico, T.; Fiorillo, C.; Galosi, S.; Lieto, M.; Malandrini, A.; Melone, M. A. B.; Mignarri, A.; Natale, G.; Pegoraro, E.; Petrucci, A.; Ricca, I.; Riso, V.; Rossi, S.; Rubegni, A.; Scarlatti, A.; Tinelli, F.; Trovato, R.; Tedeschi, G.; Tessa, A.; Filla, A.; Santorelli, F. M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1116302
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