title: Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood.
abstract: BACKGROUND
  We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood-onset recessive sensory loss associated with deafness and variable optic atrophy.
  
  
  METHODS
  Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals.
  
  
  RESULTS
  WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown-Vialetto-Van-Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement.
  
  
  CONCLUSIONS
  Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability.
authors.affiliation: Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, Montréal, Canada; Division of Pediatric Neurology, Montreal Children's Hospital-McGill University Health Center, Montréal, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Srour
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: Putorti
authors.forename: Jeremy
authors.initials: J
authors.lastname: Schwartzentruber
authors.forename: Véronique
authors.initials: V
authors.lastname: Bolduc
authors.forename: Michael Israel
authors.initials: MI
authors.lastname: Shevell
authors.forename: Chantal
authors.initials: C
authors.lastname: Poulin
authors.forename: Erin
authors.initials: E
authors.lastname: O'ferrall
authors.forename: Daniela
authors.initials: D
authors.lastname: Buhas
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
mesh_terms: D000293:Adolescent; D010244:Bulbar Palsy, Progressive / Q000178:diet therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000178:diet therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009460:Neurologic Examination; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012256:Riboflavin / Q000008:administration & dosage / Q000097:blood; D013497:Sural Nerve / Q000473:pathology; D055815:Young Adult
chemical_list: D043562:Receptors, G-Protein-Coupled; C540350:SLC52A2 protein, human; D012256:Riboflavin
keywords: Brown-Vialetto-Van Laere syndrome; SLC52A2; neuronopathy; riboflavin transporter; sensorimotor neuropathy