TY - JOUR
T1 - Pathogenicity of exonic indels in fused in sarcoma in amyotrophic lateral sclerosis
AU - Rutherford, Nicola J.
AU - Finch, Nicole A.
AU - DeJesus-Hernandez, Mariely
AU - Crook, Richard J.P.
AU - Lomen-Hoerth, Catherine
AU - Wszolek, Zbigniew K.
AU - Uitti, Ryan J.
AU - Graff-Radford, Neill R.
AU - Rademakers, Rosa
N1 - Funding Information:
ALS samples from the NINDS Human Genetics Resource Center DNA and Cell Line Repository ( ccr.coriell.org/ninds ) were included in this study. This work was supported by the ALS Association (ALSA), NIH grants R01 NS065782 , R01 AG26251-03A1 , P50 AG16574 , P50 NS40256 , and Mayo Clinic Florida Research Committee.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Deletion
KW - Fused in sarcoma
KW - Insertion
KW - Mutation
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U2 - 10.1016/j.neurobiolaging.2010.09.029
DO - 10.1016/j.neurobiolaging.2010.09.029
M3 - Article
C2 - 21074900
AN - SCOPUS:82755161970
SN - 0197-4580
VL - 33
SP - 424.e23-424.e24
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 2
ER -