We searched MEDLINE, Gene Ontology and OMIM databases to identify links to known pathways in ALS pathogenesis for CYP27A1. The CYP27A1 gene is involved in cholesterol metabolism and has been associated with cerebrotendinous xanthomatosis (CTX), which can present with progressive upper motor neuron signs and is a known clinical mimic for primary lateral sclerosis [39], [40]. Two heterozygous mutations in CYP27A1 have been reported in a patient with atypical CTX and frontotemporal dementia characteristics [41]. Furthermore, previously, serum cholesterol levels have been implicated in modifying survival and in the onset of respiratory impairment in ALS patients [42]–[44]. The combination of our results and these prior data make CYP27A1 a plausible candidate gene for ALS.
