10.3389/fgene.2018.00085.s002 Hena Ahmad Hena Ahmad Teresa Requena Teresa Requena Lidia Frejo Lidia Frejo Marien Cobo Marien Cobo Alvaro Gallego-Martinez Alvaro Gallego-Martinez Francisco Martin Francisco Martin Jose A. Lopez-Escamez Jose A. Lopez-Escamez Adolfo M. Bronstein Adolfo M. Bronstein Table_1.pdf Frontiers 2018 cerebellar ataxia vestibular hypofunction neuropathy whole-exome sequencing ETS domain 2018-03-23 04:02:56 Dataset https://frontiersin.figshare.com/articles/dataset/Table_1_pdf/6020189 <p>Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a rare disorder with an unknown etiology. We present a British family with presumed autosomal dominant CANVAS with incomplete penetrance and variable expressivity. Exome sequencing identified a rare missense variant in the ELF2 gene at chr4:g.140058846 C > T, c.10G > A, p.A4T which segregated in all affected patients. By using transduced BE (2)-M17 cells, we found that the mutated ELF2 (mt-ELF2) gene increased ATXN2 and reduced ELOVL5 gene expression, the causal genes of type 2 and type 38 spinocerebellar ataxias. Both, western blot and confocal microscopy confirmed an increase of ataxin-2 in BE(2)-M17 cells transduced with lentivirus expressing mt-ELF2 (CEE-mt-ELF2), which was not observed in cells transduced with lentivirus expressing wt-ELF2 (CEE-wt-ELF2). Moreover, we observed a significant decrease in the number and size of lipid droplets in the CEE-mt-ELF2-transduced BE (2)-M17 cells, but not in the CEE-wt-ELF2-transduced BE (2)-M17. Furthermore, changes in the expression of ELOVL5 could be related with the reduction of lipid droplets in BE (2)-M17 cells. This work supports that ELF2 gene regulates the expression of ATXN2 and ELOVL5 genes, and defines new molecular links in the pathophysiology of cerebellar ataxias.</p>