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Pathogenicity of exonic indels in fused in sarcoma in amyotrophic lateral sclerosis |
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| Authors: | Rutherford Nicola J Finch Nicole A DeJesus-Hernandez Mariely Crook Richard J P Lomen-Hoerth Catherine Wszolek Zbigniew K Uitti Ryan J Graff-Radford Neill R Rademakers Rosa |
| Affiliation: | a Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA b Department of Neurology, University of California San Francisco, San Francisco, CA, USA c Department of Neurology, Mayo Clinic, Jacksonville, FL, USA |
| Abstract: | Insertion and deletion variants (indels) within poly glycine tracts of fused in sarcoma (FUS) were initially reported as causative of disease in amyotrophic lateral sclerosis (ALS). Subsequent studies identified similar indels in controls and suggested that these indels may confer susceptibility to ALS. We aimed to elucidate the role of previously published and novel exonic indels in FUS in an extensive cohort of 630 ALS patients and 1063 controls. We detected indels in FUS exons 5, 6, 12, and 14 with similar frequencies in patients (0.95%) and controls (0.75%). Exonic indels in poly glycine tracts were also observed with similar frequencies. The largest indel (p.Gly138_Tyr143del) was observed in 1 control. In 1 patient, a 3 base pair deletion in exon 14 (p.Gly475del) was identified, however in vitro studies did not reveal abnormal localization of p.Gly475del mutant FUS. These findings suggest that not all exonic indels in FUS cause disease. |
| Keywords: | Amyotrophic lateral sclerosis Fused in sarcoma Mutation Insertion Deletion |
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