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Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations
  1. Marianna Ciccolella1,
  2. Stefania Corti2,
  3. Michela Catteruccia1,
  4. Stefania Petrini3,
  5. Giulia Tozzi1,
  6. Teresa Rizza1,
  7. Rosalba Carrozzo1,
  8. Monica Nizzardo2,
  9. Andreina Bordoni2,
  10. Dario Ronchi2,
  11. Adele D'Amico1,
  12. Cristiano Rizzo1,
  13. Giacomo Pietro Comi2,
  14. Enrico Bertini1
  1. 1Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesu’ Children's Research Hospital, Rome, Italy
  2. 2Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), Neurology Unit, University of Milan, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  3. 3Confocal Microscopy Core Facility, Bambino Gesu’ Children's Research Hospital, Rome, Italy
  1. Correspondence to Dr Enrico Bertini, Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesu’ Children's Research Hospital, P.za S. Onofrio, 4; Rome 00165, Italy; ebertini{at}tin.it

Abstract

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.

  • Neurosciences
  • Neuromuscular disease
  • Motor neurone disease
  • Metabolic disorders

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