Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations

J Med Genet. 2013 Feb;50(2):104-7. doi: 10.1136/jmedgenet-2012-101204. Epub 2012 Dec 14.


Background: Brown-Vialetto-Van Laere (BVVL) syndrome is a rare disorder characterised by progressive pontobulbar palsy and sensorineural deafness. Causative mutations in genes encoding human riboflavin transporter 2 (hRFT2) and 3 (hRFT3) have been identified in BVVL patients.

Methods and results: We report the clinical and molecular features of a severe BVVL patient in whom screening of SLC52A3/hRFT2 was negative. Sequence analysis identified two novel compound heterozygous mutations in SLC52A2/hRFT3, namely c.155C>T and c.1255G>A, leading to the amino acid changes p.S52F and p.G419S, respectively. Functional studies show that these defects impair the gene expression of the corresponding transporter, resulting in a significant reduction of riboflavin transport.

Conclusions: These findings support the pathogenetic role of SLC52A2/hRFT3 in BVVL with important clinical and therapeutic implications.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bulbar Palsy, Progressive / genetics*
  • Child, Preschool
  • DNA Mutational Analysis
  • Fatal Outcome
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Membrane Transport Proteins / genetics*
  • Molecular Sequence Data
  • Receptors, G-Protein-Coupled / genetics*
  • Sequence Alignment


  • Membrane Transport Proteins
  • Receptors, G-Protein-Coupled
  • SLC52A2 protein, human
  • SLC52A3 protein, human

Supplementary concepts

  • Brown-Vialetto-Van Laere syndrome