title: Essential Tremor in a Charcot-Marie-Tooth Type 2C Kindred Does Not Segregate with the TRPV4 R269H Mutation.
abstract: BACKGROUND
  We investigated 4 members of a family with type 2C Charcot-Marie-Tooth (CMT) and self-reported essential tremor (ET). A heterozygous missense mutation, R269H, in the TRPV4 gene was previously reported in this family. Our genotypic data provided a rare opportunity to determine the etiology of the tremor.
  
  
  METHODS
  Family study; the 4 tremor cases underwent a detailed neurological assessment.
  
  
  RESULTS
  The clinical diagnosis of ET was confirmed in all 4 tremor cases based on stringent published research criteria. Two of these also had CMT. We genotyped all 4 family members for the TRPV4 R269H mutation. We confirmed the presence of the TRPV4 R269H mutation in the 2 family members with ET and CMT; however, the TRPV4 R269H mutation did not segregate with ET in the same family.
  
  
  CONCLUSIONS
  In this particular CMT family, the tremor was clinically attributed to ET. Furthermore, genotype data indicated that the tremor was unlikely to be caused by incomplete penetrance or variable expressivity of the TRPV4 R269H mutation. Hence, the tremor likely represents ET. This establishes that in some CMT families the tremor diathesis likely represents a second disorder, namely ET.
authors.affiliation: G.H. Sergievsky Center, Columbia University, N.Y., USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, N.Y., USA ; Department of Neurology, College of Physicians and Surgeons, Columbia University, N.Y., USA ; Department of Epidemiology, Mailman School of Public Health, Columbia University, N.Y., USA.
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: G.H. Sergievsky Center, Columbia University, N.Y., USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Hernandez
authors.affiliation: G.H. Sergievsky Center, Columbia University, N.Y., USA ; Department of Neurology, College of Physicians and Surgeons, Columbia University, N.Y., USA ; Department of Epidemiology, Mailman School of Public Health, Columbia University, N.Y., USA ; Division of Epidemiology, New York State Psychiatric Institute, New York, N.Y., USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, N.Y., USA.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Ionita-Laza
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, N.Y., USA ; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, N.Y., USA.
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
keywords: Charcot-Marie-Tooth; Essential tremor; Genetics; Neuropathy