NGS in Hereditary Ataxia: When Rare Becomes Frequent

被引：24

作者：

Galatolo, Daniele ^{[1
]}

De Michele, Giovanna ^{[2
]}

Silvestri, Gabriella ^{[3
,4
]}

Leuzzi, Vincenzo ^{[5
]}

Casali, Carlo ^{[6
]}

Musumeci, Olimpia ^{[7
]}

Antenora, Antonella ^{[2
]}

Astrea, Guja ^{[1
]}

Barghigiani, Melissa ^{[1
]}

Battini, Roberta ^{[1
]}

Battisti, Carla ^{[8
]}

Caputi, Caterina ^{[5
]}

Cioffi, Ettore ^{[6
]}

De Michele, Giuseppe ^{[2
]}

Dotti, Maria Teresa ^{[8
]}

Fico, Tommasina ^{[2
]}

Fiorillo, Chiara ^{[9
,10
]}

Galosi, Serena ^{[5
]}

Lieto, Maria ^{[2
]}

Malandrini, Alessandro ^{[8
]}

Melone, Marina A. B. ^{[11
,12
]}

Mignarri, Andrea ^{[8
]}

Natale, Gemma ^{[1
]}

Pegoraro, Elena ^{[13
]}

Petrucci, Antonio ^{[14
]}

Ricca, Ivana ^{[1
]}

Riso, Vittorio ^{[3
,4
]}

Rossi, Salvatore ^{[3
,4
]}

Rubegni, Anna ^{[1
]}

Scarlatti, Arianna ^{[1
]}

Tinelli, Francesca ^{[1
]}

Trovato, Rosanna ^{[1
]}

Tedeschi, Gioacchino ^{[11
,12
]}

Tessa, Alessandra ^{[1
]}

Filla, Alessandro ^{[2
]}

Santorelli, Filippo Maria ^{[1
]}

机构：

[1] IRCCS Stella Maris Fdn, Mol Med Neurodegenerat & Neuromuscular Dis Unit, I-56128 Pisa, Italy

[2] Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, I-80131 Naples, Italy

[3] Fdn Policlin Univ A Gemelli IRCCS, UOC Neurol, I-00168 Rome, Italy

[4] Univ Cattolica Sacro Cuore, Dept Neurosci, I-00168 Rome, Italy

[5] Sapienza Univ Rome, Dept Human Neurosci, I-00185 Rome, Italy

[6] Sapienza Univ Rome, Dept Med & Surg Sci & Biotechnol, I-40100 Latina, Italy

[7] Univ Messina, Dept Clin & Expt Med, Unit Neurol & Neuromuscular Disorders, I-98122 Messina, Italy

[8] Univ Siena, Dept Med, Surg & Neurosci, I-53100 Siena, Italy

[9] Univ Genoa, Paediat Neurol & Muscular Dis Unit, I-16147 Genoa, Italy

[10] G Gaslini Inst Children, I-16147 Genoa, Italy

[11] Univ Campania Luigi Vanvitelli, Ctr Rare Dis, I-80131 Naples, Italy

[12] Univ Campania Luigi Vanvitelli, Interuniv Ctr Res Neurosci, Dept Adv Med & Surg Sci, Div Neurol 2, I-80131 Naples, Italy

[13] Univ Padua, Dept Neurosci, I-35121 Padua, Italy

[14] Azienda Osped San Camillo Forlanini, I-00152 Rome, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 16期

关键词：

HA; next-generation sequencing; cohort; targeted resequencing panel; TRP; exome sequencing; diagnostic yield; variant; mutation; Genesis; PROGRESSIVE CEREBELLAR-ATAXIA; AUTOSOMAL-DOMINANT; MUTATIONS CAUSE; MOLECULAR CHARACTERIZATION; SPASTIC PARAPLEGIA; POLG MUTATIONS; ADULT-ONSET; GENE; DISORDERS; PHENOTYPE;

D O I：

10.3390/ijms22168490

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：23

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