Brown−Vialetto−Van Laere and Fazio−Londe syndromes: <i>SLC52A3</i> mutations with puzzling phenotypes and inheritance

Background Brown−Vialetto−Van Laere syndrome (BVVLS) and Fazio−Londe disease (FLD) are rare neurological disorders presenting with pontobulbar palsy, muscle weakness respiratory insufficiency. Mutations in SLC52A2 (hRFVT-2) or SLC52A3 (hRFVT-3) genes can be responsible for these an autosomal recessive pattern of inheritance. The aim this study was to screen mutations among Indian families diagnosed BVVLS FLD. Methods were screened one FLD three patients by exon-specific amplification using PCR sequencing. In silico predictions bioinformatics tools confocal imaging HEK-293 cells performed determine the functional impact identified mutations. Results Genetic analysis a mother son novel homozygous mutation c.710C>T (p.Ala237Val) SLC52A3. This variant found have pseudodominant inheritance, which neither listed Exome Variant Server 1000 Genomes Project database. p.Ala237Val showed higher degree disorderness hRFVT-3 that could affect riboflavin transport. Furthermore, common c.62A>G (p.Asn21Ser) other patients. Despite having different clinical phenotypes, both attributed mutation. Conclusion A peculiar inheritance is observed first time two genetically related cases origin variable phenotypes.