Evaluating Familial Essential Tremor with Novel Genetic Approaches: Is it a Genotyping or Phenotyping Issue?
BACKGROUND
Essential tremor is a common movement disorder with a strong heritable component. Large families with inherited forms of essential tremor have undergone genetic analyses by different approaches. However, our knowledge of genetic variants unequivocally linked to essential tremor is remarkably limited. Several explanations have been put forth to explain this challenge, including the possibility of mutations in non-coding areas of the genome.


METHODS
We encountered a family with highly penetrant, autosomal dominant tremor. We hypothesized that, if a single coding gene mutation was responsible for the phenotype, novel genetic tools would allow us to identify it. We employed single nucleotide polymorphism (SNP) arrays in 17 members of this family followed by next generation whole-exome sequencing in five affected subjects.


RESULTS
We did not identify any copy number variant or mutation that segregated with the disease phenotype.


CONCLUSIONS
This study emphasizes the remarkably challenging field of tremor genetics and indicates that future studies should perhaps shift to analysis of the non-coding genome.
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Pedro
P
Gonzalez-Alegre
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Jorge
J
Di Paola
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Kai
K
Wang
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Shay
S
Fabbro
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Hung-Chun
HC
Yu
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Tamim H
TH
Shaikh
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Benjamin W
BW
Darbro
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA ; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Alexander G
AG
Bassuk
Essential tremor; dystonia; genetics