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.
No C9orf72 repeat expansion in patients with primary progressive multiple sclerosis / C. Tiloca, M. Sorosina, F. Esposito, S. Peroni, C. Colombrita, N. Ticozzi, A. Ratti, F. Martinelli Boneschi, V. Silani. - In: MULTIPLE SCLEROSIS AND RELATED DISORDERS. - ISSN 2211-0348. - 25(2018), pp. 192-195.
|Titolo:||No C9orf72 repeat expansion in patients with primary progressive multiple sclerosis|
SILANI, VINCENZO (Corresponding)
|Parole Chiave:||Amyotrophic lateral sclerosis; C9orf72; Frontotemporal dementia; Intermediate alleles; Primary progressive multiple sclerosis; Neurology; Neurology (clinical)|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
Settore MED/03 - Genetica Medica
Settore BIO/18 - Genetica
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.msard.2018.07.047|
|Appare nelle tipologie:||01 - Articolo su periodico|