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Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis

Cinzia Tiloca1, Antonia Ratti, Viviana Pensato

  • 1Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy.

Neurobiology of Aging
|December 6, 2011
PubMed

Insights

Valosin-containing protein (VCP) gene mutations are not a primary cause of familial amyotrophic lateral sclerosis (ALS) in the Italian population. This study screened VCP in ALS and ALS-frontotemporal dementia (FTD) patients, finding no significant contribution.

Area of Science:

  • Genetics
  • Neurodegenerative Diseases
  • Molecular Biology

Background:

  • Valosin-containing protein (VCP) gene mutations are linked to inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD).
  • Recent findings suggest VCP mutations may also occur in familial amyotrophic lateral sclerosis (ALS).

Purpose of the Study:

  • To investigate the frequency of VCP gene mutations in the Italian population affected by familial ALS and ALS-frontotemporal dementia (FTD).

Main Methods:

  • Screening of 166 familial ALS and 14 ALS-FTD individuals for VCP gene mutations.
  • Identification of specific mutations and variants, including a synonymous mutation, intronic variants, and a 3' untranslated region (UTR) nucleotide change.
  • Bioinformatical analysis to predict the impact of identified variants on splicing and microRNA binding.

Main Results:

  • A previously reported synonymous mutation (c.2093A>C; p.Q568Q) was identified.
  • Two intronic variants (c.1749-14C>T; c.2085-3C>T) and a 3' UTR nucleotide change (c.2814G>T) were also found.
  • Bioinformatical predictions indicated no significant alterations in splicing or microRNA binding sites.

Conclusions:

  • The study did not find evidence supporting a major role of VCP gene mutations in familial ALS within the Italian cohort.
  • The identified variants were either previously known or predicted to have no functional impact.

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