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

2012; BMJ; Volume: 50; Issue: 2 Linguagem: Inglês

10.1136/jmedgenet-2012-101204

1468-6244

Marianna Ciccolella, Stefania Corti, Michela Catteruccia, Stefania Petrini, Giulia Tozzi, Teresa Rizza, Rosalba Carrozzo, Monica Nizzardo, Andreina Bordoni, Dario Ronchi, Adele D’Amico, Cristiano Rizzo, Giacomo P. Comi, Enrico Bertini,

DNA and Nucleic Acid Chemistry

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.