Abstract |
Brown-Vialetto-Van Laere syndrome (BVVLS [MIM 211530]) is a rare neurological disorder characterized by infancy onset sensorineural deafness and ponto- bulbar palsy. Mutations in SLC52A3 (formerly C20orf54), coding for riboflavin transporter 2 (hRFT2), have been identified as the molecular genetic correlate in several individuals with BVVLS. Exome sequencing of just one single case revealed that compound heterozygosity for two pathogenic mutations in the SLC52A2 gene coding for riboflavin transporter 3 (hRFT3), another member of the riboflavin transporter family, is also associated with BVVLS. Overexpression studies confirmed that the gene products of both mutant alleles have reduced riboflavin transport activities. While mutations in SLC52A3 cause decreased plasma riboflavin levels, concordant with a role of SLC52A3 in riboflavin uptake from food, the SLC52A2-mutant individual had normal plasma riboflavin concentrations, a finding in line with a postulated function of SLC52A2 in riboflavin uptake from blood into target cells. Our results contribute to the understanding of human riboflavin metabolism and underscore its role in the pathogenesis of BVVLS, thereby providing a rational basis for a high-dose riboflavin treatment.
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Authors | Tobias B Haack, Christine Makowski, Yoshiaki Yao, Elisabeth Graf, Maja Hempel, Thomas Wieland, Ulrike Tauer, Uwe Ahting, Johannes A Mayr, Peter Freisinger, Hiroki Yoshimatsu, Ken Inui, Tim M Strom, Thomas Meitinger, Atsushi Yonezawa, Holger Prokisch |
Journal | Journal of inherited metabolic disease
(J Inherit Metab Dis)
Vol. 35
Issue 6
Pg. 943-8
(Nov 2012)
ISSN: 1573-2665 [Electronic] United States |
PMID | 22864630
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Transport Proteins
- Nerve Tissue Proteins
- Receptors, G-Protein-Coupled
- SLC52A2 protein, human
- SLC52A3 protein, human
- Riboflavin
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Topics |
- Amino Acid Sequence
- Base Sequence
- Biological Transport, Active
(genetics)
- Bulbar Palsy, Progressive
(diagnosis, genetics, metabolism)
- Child, Preschool
- DNA Mutational Analysis
- Female
- Hearing Loss, Sensorineural
(diagnosis, genetics, metabolism)
- Humans
- Membrane Transport Proteins
(deficiency, genetics, metabolism)
- Models, Biological
- Molecular Sequence Data
- Mutation, Missense
- Nerve Tissue Proteins
(deficiency, genetics, metabolism)
- Receptors, G-Protein-Coupled
(deficiency, genetics, metabolism)
- Riboflavin
(metabolism)
- Sequence Homology, Amino Acid
- Syndrome
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