title: Utility of whole exome sequencing in evaluation of juvenile motor neuron disease.
abstract: BACKGROUND
  This case report focuses on identifying novel mutations in juvenile motor neuron disease and emphasizes the significance of whole exome sequencing (WES).
  
  
  METHODS
  We report a 13-year-old Hispanic boy with rapidly progressive weakness, muscle atrophy, tremor, and tongue fasciculation, along with upper motor neuron findings of hyperactive gag reflex, hyperreflexia, and cog-wheel rigidity. Electromyography was suggestive of motor neuron disease. After an extensive evaluation, WES was performed.
  
  
  RESULTS
  WES identified a heterozygous de novo variant of unknown clinical significance (VUS) in the fused-in-sarcoma gene (FUS) [c.1554_1557del]. Although initially reported as a VUS, the clinical data from our patient and data from the medical literature support that the variant is indeed disease-causing.
  
  
  CONCLUSIONS
  The genetic etiology of amyotrophic lateral sclerosis (ALS) is heterogeneous and, as clinical sequencing for FUS was not available, WES was the only method by which a diagnosis of juvenile ALS could be made.
authors.affiliation: Department of Pediatric Neurology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, 77030, USA.
authors.forename: Sonika
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Potocki
authors.affiliation: Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Talia R
authors.initials: TR
authors.lastname: Collier
authors.affiliation: Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Woodbury
authors.affiliation: Department of Pathology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.affiliation: Department of Radiology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.affiliation: Department of Pediatric Neurology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, 77030, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Lotze
mesh_terms: D000293:Adolescent; D059472:Exome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D016472:Motor Neuron Disease / Q000175:diagnosis* / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS
keywords: fused-in-sarcoma (FUS) gene; genetics; juvenile amyotrophic lateral sclerosis; motor neuron disease; spasticity; weakness; whole exome sequencing