title: SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere Syndrome in an Indian patient: First genetically proven case with mutations in two riboflavin transporters.
abstract: BACKGROUND
  Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by bulbar palsies and sensorineural deafness, is mainly associated with defective riboflavin transporters encoded by the SLC52A2 and SLC52A3 genes.
  
  
  METHODS
  Here we present a 16-year-old BVVLS patient belonging to a five generation consanguineous family from Indian ethnicity with two homozygous missense mutations viz., c.421C>A [p.P141T] in SLC52A2 and c.62A>G [p.N21S] in SLC52A3.
  
  
  RESULTS
  Functional characterization based on3H-riboflavin uptake assay and live-cell confocal imaging revealed that the effect of mutation c.421C>A [p.P141T] identified in SLC52A2 had a slight reduction in riboflavin uptake; on the other hand, the c.62A>G [p.N21S] identified in SLC52A3 showed a drastic reduction in riboflavin uptake, which appeared to be due to impaired trafficking and membrane targeting of the hRFVT-3 protein.
  
  
  CONCLUSIONS
  This is the first report presenting mutations in both riboflavin transporters hRFVT-2 and hRFVT-3 in the same BVVLS patient. Also, c.62A>G [p.N21S] in SLC52A3 appears to contribute more to the disease phenotype in this patient than c.421C>A [p.P141T] in SLC52A2.
authors.affiliation: School of Biotechnology, Madurai Kamaraj University, Madurai 625021, India.
authors.forename: Tamilarasan
authors.initials: T
authors.lastname: Udhayabanu
authors.affiliation: Departments of Medicine, Physiology/Biophysics, University of California, Irvine, CA 92697, USA; Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
authors.forename: Veedamali S
authors.initials: VS
authors.lastname: Subramanian
authors.affiliation: Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Teafatiller
authors.affiliation: Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
authors.forename: Vykuntaraju K
authors.initials: VK
authors.lastname: Gowda
authors.affiliation: Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
authors.forename: Varun S
authors.initials: VS
authors.lastname: Raghavan
authors.affiliation: School of Biotechnology, Madurai Kamaraj University, Madurai 625021, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Varalakshmi
authors.affiliation: Departments of Medicine, Physiology/Biophysics, University of California, Irvine, CA 92697, USA; Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
authors.affiliation: School of Biotechnology, Madurai Kamaraj University, Madurai 625021, India. Electronic address: rbashokkumar@yahoo.com.
authors.forename: Balasubramaniem
authors.initials: B
authors.lastname: Ashokkumar
mesh_terms: D000293:Adolescent; D010244:Bulbar Palsy, Progressive / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007194:India; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012256:Riboflavin / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D043562:Receptors, G-Protein-Coupled; C540350:SLC52A2 protein, human; C548553:SLC52A3 protein, human; D012256:Riboflavin
keywords: BVVLS; Motor neuronopathy; hRFVT-2; hRFVT-3