title: Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar-onset neuropathy.
abstract: BACKGROUND
  Progressive bulbar motor neuropathy is primarily caused by bulbar-onset ALS. Hereditary amyloidosis type IV also presents with a bulbar neuropathy that mimics motor neuron disease. The disease is prevalent in Finland only and is not commonly included in the differential diagnosis of ALS.
  
  
  METHODS
  We studied 18 members of a family in which some had bulbar motor neuropathy, and we performed exome sequencing.
  
  
  RESULTS
  Five affected family members were found to have a D187Y substitution in the GSN gene known to cause hereditary amyloidosis type IV.
  
  
  CONCLUSIONS
  This American family presented with progressive bulbar neuropathy due to a gelsolin mutation not found in Finland. Hereditary amyloidosis type IV presents with bulbar motor neuropathy and not with peripheral neuropathy as occurs with common forms of amyloidosis. This report demonstrates the power of exome sequencing to determine the cause of rare hereditary diseases with incomplete or atypical phenotypes. Muscle Nerve 56: 1001-1005, 2017.
authors.affiliation: Department of Neurology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina, 27157, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Caress
authors.affiliation: Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, United Kingdom.|Neuromuscular Diseases Research Section Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yevgeniya A
authors.initials: YA
authors.lastname: Abramzon
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.affiliation: Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.|Department of Molecular Neuroscience, MRC Centre for Neuromuscular Diseases and the Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, Queen Square, London, United Kingdom.
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.affiliation: Neurology Associates, Merit Health Medical Group, Hattiesburg, Mississippi, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sullivan
authors.affiliation: Neurological Associates, New Westminster, BC, Canada, V3L 3W4.
authors.forename: Chamanpreet S
authors.initials: CS
authors.lastname: Chahal
authors.affiliation: Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D000369:Aged, 80 and over; D028226:Amyloidosis, Familial / Q000150:complications / Q000235:genetics*; D010244:Bulbar Palsy, Progressive / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018260:Gelsolin / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
chemical_list: D018260:Gelsolin
keywords: amyloidosis; amyotrophic lateral sclerosis; bulbar neuropathy; corneal dystrophy; exome sequencing; gelsolin; motor neuron disease