Genetic analysis of SIGMAR1 as a cause of familial ALS with dementia

Véronique V. Belzil, Hussein Daoud, William Camu, Michael J. Strong, Patrick A. Dion, Guy A. Rouleau

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Amyotrophic lateral sclerosis (ALS) is the most common motor neuron diseases (MND), while frontotemporal lobar degeneration (FTLD) is the second most common cause of early-onset dementia. Many ALS families segregating FTLD have been reported, particularly over the last decade. Recently, mutations in TARDBP, FUS/TLS, and C9ORF72 have been identified in both ALS and FTLD patients, while mutations in VCP, a FTLD associated gene, have been found in ALS families. Distinct variants located in the 3′-untranslated region (UTR) of the SIGMAR1 gene were previously reported in three unrelated FTLD or FTLD-MND families. We directly sequenced the coding and UTR regions of the SIGMAR1 gene in a targeted cohort of 25 individual familial ALS cases of Caucasian origin with a history of cognitive impairments. This screening identified one variant in the 3′-UTR of the SIGMAR1 gene in one ALS patient, but the same variant was also observed in 1 out of 380 control chromosomes. Subsequently, we screened the same samples for a C9ORF72 repeat expansion: 52% of this cohort was found expanded, including the sample with the SIGMAR1 3′-UTR variant. Consequently, coding and noncoding variants located in the 3′-UTR region of the SIGMAR1 gene are not the cause of FTLD-MND in our cohort, and more than half of this targeted cohort is genetically explained by C9ORF72 repeat expansions.

Original languageEnglish (US)
Pages (from-to)237-239
Number of pages3
JournalEuropean Journal of Human Genetics
Issue number2
StatePublished - Feb 2013


  • Amyotrophic lateral sclerosis
  • dementia
  • frontotemporal lobar degeneration
  • motor neuron disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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