2. Academic Validation
  3. 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

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

  • Clin Chim Acta. 2016 Nov 1;462:210-214. doi: 10.1016/j.cca.2016.09.022.
Tamilarasan Udhayabanu 1,  Veedamali S Subramanian 2,  Trevor Teafatiller 3,  Vykuntaraju K Gowda 4,  Varun S Raghavan 4,  Perumal Varalakshmi 1,  Hamid M Said 2,  Balasubramaniem Ashokkumar 5
Affiliations

Affiliations

  • 1 School of Biotechnology, Madurai Kamaraj University, Madurai 625021, India.
  • 2 Departments of Medicine, Physiology/Biophysics, University of California, Irvine, CA 92697, USA; Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
  • 3 Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
  • 4 Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
  • 5 School of Biotechnology, Madurai Kamaraj University, Madurai 625021, India. Electronic address: rbashokkumar@yahoo.com.
PMID: 27702554 DOI: 10.1016/j.cca.2016.09.022
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 on 3H-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.

Keywords

BVVLS; Motor neuronopathy; hRFVT-2; hRFVT-3.

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