Highlights
- •TARDBP Ala382Thr mutation and C9orf72 expansion are pathogenic in some neurodegenerative diseases.
- •We evaluated the frequency of these mutations in a cohort of MS patients and controls from Sardinia.
- •Information of these genetic mutations will increase knowledge about neurodegeneration in MS.
Abstract
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized
by inflammation and accompanied and followed by neurodegeneration. Missense mutations
of the TAR DNA Binding Protein gene (TARDBP) located in the chromosome 1p36.22 region,
and the hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72)
are pathogenic in other neurodegenerative diseases such as amyotrophic lateral sclerosis
and frontotemporal lobar degeneration. Assuming that TARDBP Ala382Thr mutation and
C9orf72 expansion may underlie MS, we evaluated their frequency in a large cohort
of MS patients and controls from Sardinia, an island characterized by a very high
frequency of MS and an unusual genetic background.
Genomic DNA was extracted from peripheral blood and analyzed for the presence of a
TARDBP Ala382Thr mutation and C9orf72 expansion. Difference in the frequency of these
mutations between MS patients and controls was calculated using the χ2 test with a standard 2 × 2 table. The Ala382Thr mutation in its heterozygous state was found in 27/1833 patients
(1.4%) and 20/1475 controls (1.3%), whereas C9orf72 pathogenic repeat expansion was
found in 6/1014 MS patients (0.6%) and 2/333 controls (0.6%). Individuals carrying
the mutations did not present with other neurodegenerative conditions and any differences
were reported between groups.
TARDBP Ala382Thr mutation and C9orf72 expansion do not play a major role in MS pathogenesis
in the Sardinian population. Further analyses on larger samples of MS patients from
other populations are needed to better define the possible role of these genes in
the complex interplay between neuroinflammation and neurodegeneration in MS.
Keywords
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Article info
Publication history
Published online: July 23, 2015
Accepted:
July 22,
2015
Received in revised form:
July 5,
2015
Received:
April 30,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
