No C9orf72 repeat expansion in patients with primary progressive multiple sclerosis

Cinzia Tiloca, Melissa Sorosina, Federica Esposito, Silvia Peroni, Claudia Colombrita, Nicola Ticozzi, Antonia Ratti, Filippo Martinelli Boneschi, Vincenzo Silani

Research output: Contribution to journalArticle

Abstract

Pathological repeat expansion (RE) of the C9orf72 hexanucleotide sequence is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia disease continuum, although other heterogeneous clinical phenotypes have been documented. The occurrence of multiple sclerosis (MS) in some C9orf72 carriers with a more severe ALS disease course has suggested a possible modifying role for MS. However, C9orf72 RE seems not to play a role in MS pathogenesis. In this study, we screened C9orf72 in 189 Italian patients with primary progressive MS (PPMS), a rare clinical form characterized by less inflammation over neurodegenerative features. We failed to detect C9orf72 RE, but a significant representation of intermediate alleles (≥ 20 units) was observed in our PPMS cohort (2.1%) compared to healthy controls (0%, p < 0.05). In the normal range, allele distribution showed a trimodal pattern (2,5,8-repeat units) in PPMS and healthy controls with no significant difference. Our findings further demonstrate that C9orf72 RE is not genetically associated to MS spectrum, but suggest that intermediate alleles may represent risk factors as already reported for Parkinson disease.

Original languageEnglish
Pages (from-to)192-195
Number of pages4
JournalMultiple Sclerosis and Related Disorders
Volume25
DOIs
Publication statusPublished - Oct 1 2018

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Chronic Progressive Multiple Sclerosis
Multiple Sclerosis
Alleles
Amyotrophic Lateral Sclerosis
Parkinson Disease
Reference Values
Inflammation
Phenotype

Keywords

  • Amyotrophic lateral sclerosis
  • C9orf72
  • Frontotemporal dementia
  • Intermediate alleles
  • Primary progressive multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

No C9orf72 repeat expansion in patients with primary progressive multiple sclerosis. / Tiloca, Cinzia; Sorosina, Melissa; Esposito, Federica; Peroni, Silvia; Colombrita, Claudia; Ticozzi, Nicola; Ratti, Antonia; Boneschi, Filippo Martinelli; Silani, Vincenzo.

In: Multiple Sclerosis and Related Disorders, Vol. 25, 01.10.2018, p. 192-195.

Research output: Contribution to journalArticle

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AU - Tiloca, Cinzia

AU - Sorosina, Melissa

AU - Esposito, Federica

AU - Peroni, Silvia

AU - Colombrita, Claudia

AU - Ticozzi, Nicola

AU - Ratti, Antonia

AU - Boneschi, Filippo Martinelli

AU - Silani, Vincenzo

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