Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeat expansion in C9orf72 gene (C9orf72-HRE) is the most frequent genetic cause of ALS. Since many ALS pedigrees showed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72-HRE patients with contrasting findings. To disclose the possible role of NIPA1 GCG repeat length as modifier of the disease risk in C9orf72-HRE carriers, we analyzed a large cohort of 532 Italian ALS cases enriched in C9orf72-HRE carriers (172 cases) and 483 Italian controls. This sample size is powered (92% power, p = 0.05) to replicate the modifier effect observed in literature. We did not observe higher frequency of NIPA1 long alleles (> 8 GCG) in C9orf72-HRE carriers (3.5%) compared with C9orf72-HRE negative patients (4.1%) and healthy controls (5%). For the latter comparison, we meta-analyzed our data with currently available literature data, and no statistically significant effect was observed (p = 0.118). In conclusion, we did not confirm a role of NIPA1 repeat length as a modifier of the C9orf72 ALS disease risk.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology - 40(2019), 12 vom: 08. Dez., Seite 2537-2540 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Corrado, Lucia [VerfasserIn] |
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| Links: |
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| Themen: |
ALS |
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| Anmerkungen: |
Date Completed 27.04.2020 Date Revised 27.04.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10072-019-04001-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM298996383 |
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| 245 | 1 | 0 | |a Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeat expansion in C9orf72 gene (C9orf72-HRE) is the most frequent genetic cause of ALS. Since many ALS pedigrees showed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72-HRE patients with contrasting findings. To disclose the possible role of NIPA1 GCG repeat length as modifier of the disease risk in C9orf72-HRE carriers, we analyzed a large cohort of 532 Italian ALS cases enriched in C9orf72-HRE carriers (172 cases) and 483 Italian controls. This sample size is powered (92% power, p = 0.05) to replicate the modifier effect observed in literature. We did not observe higher frequency of NIPA1 long alleles (> 8 GCG) in C9orf72-HRE carriers (3.5%) compared with C9orf72-HRE negative patients (4.1%) and healthy controls (5%). For the latter comparison, we meta-analyzed our data with currently available literature data, and no statistically significant effect was observed (p = 0.118). In conclusion, we did not confirm a role of NIPA1 repeat length as a modifier of the C9orf72 ALS disease risk | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a ALS | |
| 650 | 4 | |a C9orf72-HRE carriers | |
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| 650 | 7 | |a C9orf72 protein, human |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a NIPA1 protein, human |2 NLM | |
| 700 | 1 | |a Brunetti, Maura |e verfasserin |4 aut | |
| 700 | 1 | |a Di Pierro, Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Barberis, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Croce, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Bersano, Enrica |e verfasserin |4 aut | |
| 700 | 1 | |a De Marchi, Fabiola |e verfasserin |4 aut | |
| 700 | 1 | |a Zuccalà, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Barizzone, Nadia |e verfasserin |4 aut | |
| 700 | 1 | |a Calvo, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Moglia, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Mazzini, Letizia |e verfasserin |4 aut | |
| 700 | 1 | |a Chiò, Adriano |e verfasserin |4 aut | |
| 700 | 1 | |a D'Alfonso, Sandra |e verfasserin |4 aut | |
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