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 language | English |
|---|---|
| Pages (from-to) | 192-195 |
| Number of pages | 4 |
| Journal | Multiple Sclerosis and Related Disorders |
| Volume | 25 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - No C9orf72 repeat expansion in patients with primary progressive multiple sclerosis
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
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - C9orf72
KW - Frontotemporal dementia
KW - Intermediate alleles
KW - Primary progressive multiple sclerosis
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UR - http://www.scopus.com/inward/citedby.url?scp=85051129937&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2018.07.047
DO - 10.1016/j.msard.2018.07.047
M3 - Article
C2 - 30099204
AN - SCOPUS:85051129937
VL - 25
SP - 192
EP - 195
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
ER -