title: Whole-exome sequencing as a diagnostic tool in a family with episodic ataxia type 1.
abstract: Complex neurologic phenotypes are inherently difficult to diagnose. Whole-exome sequencing (WES) is a new tool in the neurologist's diagnostic armamentarium. Whole-exome sequencing can be applied to investigate the "diagnostic odyssey" cases. These cases involve patients with rare diseases that likely have a genetic etiology but have failed to be diagnosed by clinical evaluation and targeted gene testing. We describe such a case, a 22-year-old man who had mild intellectual developmental disability and episodes of jerking ataxic movements that affected his whole body. He underwent numerous multidisciplinary and multicentric evaluations throughout his life that failed to establish a clear diagnosis. Following his visit to Mayo Clinic in Jacksonville, Florida, WES was applied for genetic determination of the unknown disorder in the proband and his biological parents and sister. Additional clinical evaluation, magnetic resonance neuroimaging, electromyography, and electroencephalography of the proband were performed to verify the phenotype after the WES results were available. To our knowledge, this is the first report of the application of WES to facilitate the diagnosis of episodic ataxia type 1. This case illustrates that WES supported by clinical data is a useful and time-saving tool in the evaluation of patients with rare and complex hereditary disorders.
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL.
authors: Pawel
authors: P
authors: Tacik
authors: Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL.
authors: Kimberly J
authors: KJ
authors: Guthrie
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL.
authors: Audrey J
authors: AJ
authors: Strongosky
authors: Department of Radiology, Mayo Clinic, Jacksonville, FL.
authors: Daniel F
authors: DF
authors: Broderick
authors: Department of Medical Genetics, Mayo Clinic, Jacksonville, FL.
authors: Douglas L
authors: DL
authors: Riegert-Johnson
authors: Ambry Genetics Corp, Aliso Viejo, CA.
authors: Sha
authors: S
authors: Tang
authors: Ambry Genetics Corp, Aliso Viejo, CA.
authors: Dima
authors: D
authors: El-Khechen
authors: Center for Individualized Medicine, Mayo Clinic, Jacksonville, FL.
authors: Alexander S
authors: AS
authors: Parker
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors: Owen A
authors: OA
authors: Ross
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL. Electronic address: Wszolek.Zbigniew@mayo.edu.
authors: Zbigniew K
authors: ZK
authors: Wszolek
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics*; D001483:Base Sequence; D004569:Electroencephalography; D004576:Electromyography; D059472:Exome; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D020385:Myokymia / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000086:Acetazolamide