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Neurological Sciences

, Volume 40, Issue 12, pp 2537–2540 | Cite as

Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort

  • Lucia CorradoEmail author
  • Maura Brunetti
  • Alice Di Pierro
  • Marco Barberis
  • Roberta Croce
  • Enrica Bersano
  • Fabiola De Marchi
  • Miriam Zuccalà
  • Nadia Barizzone
  • Andrea Calvo
  • Cristina Moglia
  • Letizia Mazzini
  • Adriano Chiò
  • Sandra D’Alfonso
Original Article

Abstract

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.

Keywords

ALS NIPA1 C9orf72-HRE carriers 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical standards

Informed consent was obtained from all individual participants involved in the study. The informed consent was approved by the ethical committees of the local hospitals.

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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Lucia Corrado
    • 1
    Email author
  • Maura Brunetti
    • 2
  • Alice Di Pierro
    • 1
  • Marco Barberis
    • 2
  • Roberta Croce
    • 1
  • Enrica Bersano
    • 3
  • Fabiola De Marchi
    • 3
  • Miriam Zuccalà
    • 1
  • Nadia Barizzone
    • 1
  • Andrea Calvo
    • 4
    • 5
    • 6
  • Cristina Moglia
    • 4
    • 5
  • Letizia Mazzini
    • 3
  • Adriano Chiò
    • 4
    • 5
    • 6
  • Sandra D’Alfonso
    • 1
  1. 1.Department of Health SciencesUniversity of Eastern Piedmont (UPO)NovaraItaly
  2. 2.“Rita Levi Montalcini” Department of Neuroscience, Neurology II, ALS CenterUniversity of TorinoTorinoItaly
  3. 3.ALS Center AOU Maggiore della CaritàNovaraItaly
  4. 4.ALS Center, “Rita Levi Montalcini” Department of NeuroscienceUniversity of TorinoTorinoItaly
  5. 5.The Azienda Ospedaliero Universitaria Città della Salute e della Scienza di TorinoTorinoItaly
  6. 6.The Neuroscience Institute of TorinoTorinoItaly

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