TY - JOUR
T1 - Exome sequencing identifies FUS mutations as a cause of essential tremor
AU - Merner, Nancy D.
AU - Girard, Simon L.
AU - Catoire, Hélène
AU - Bourassa, Cynthia V.
AU - Belzil, Véronique V.
AU - Rivière, Jean Baptiste
AU - Hince, Pascale
AU - Levert, Annie
AU - Dionne-Laporte, Alexandre
AU - Spiegelman, Dan
AU - Noreau, Anne
AU - Diab, Sabrina
AU - Szuto, Anna
AU - Fournier, Hélène
AU - Raelson, John
AU - Belouchi, Majid
AU - Panisset, Michel
AU - Cossette, Patrick
AU - Dupré, Nicolas
AU - Bernard, Geneviève
AU - Chouinard, Sylvain
AU - Dion, Patrick A.
AU - Rouleau, Guy A.
N1 - Funding Information:
N.D.M. is the recipient of a Claude Laberge fellowship from the Réseau de Médecine Génétique Appliqué (RMGA). The RMGA also supports the bioinformatics analytical team of G.A.R. G.A.R. holds the Canada Research Chair in Genetics of the Nervous System. This work was supported by the Chaire Jeanne-et-J.-Louis-Lévesque en Génétique des Maladies du Cerveau de l’Université de Montréal.
PY - 2012/8/10
Y1 - 2012/8/10
N2 - Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290 mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
AB - Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290 mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
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U2 - 10.1016/j.ajhg.2012.07.002
DO - 10.1016/j.ajhg.2012.07.002
M3 - Article
C2 - 22863194
AN - SCOPUS:84864931903
SN - 0002-9297
VL - 91
SP - 313
EP - 319
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -