Tamilarasan Udhayabanu1, Veedamali S Subramanian2, Trevor Teafatiller3, Vykuntaraju K Gowda4, Varun S Raghavan4, Perumal Varalakshmi1, Hamid M Said2, Balasubramaniem Ashokkumar5. 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.
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.
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.
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