RT Journal Article
T1 Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family.
A1 Ahmad, Hena
A1 Requena, Teresa
A1 Frejo, Lidia
A1 Cobo, Marien
A1 Gallego-Martinez, Alvaro
A1 Martin, Francisco
A1 Lopez-Escamez, Jose A
A1 Bronstein, Adolfo M
K1 ETS domain
K1 cerebellar ataxia
K1 neuropathy
K1 vestibular hypofunction
K1 whole-exome sequencing
AB 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.
SN 1664-8021
YR 2018
FD 2018-03-23
LK https://hdl.handle.net/10668/28430
UL https://hdl.handle.net/10668/28430
LA en
DS RISalud
RD Apr 4, 2025