Imperial College London
Alternate

ProfessorAdolfoBronstein

Faculty of Medicine, Department of Brain Sciences

Emeritus Clinical Professor Head of Neuro-otology Unit
 
 
 
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Contact

 

+44 (0)20 3313 5525a.bronstein

 
 
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Assistant

 

Miss Lorna Stevenson +44 (0)20 3313 5525

 
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Location

 

10 L15bLab BlockCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ahmad:2018:10.3389/fgene.2018.00085,
author = {Ahmad, H and Requena, T and Frejo, L and Cobo, M and Gallego-Martinez, A and Martin, F and Lopez-Escamez, JA and Bronstein, AM},
doi = {10.3389/fgene.2018.00085},
journal = {Frontiers in Genetics},
title = {Clinical and functional characterization of a missense ELF2 variant in a CANVAS Family},
url = {http://dx.doi.org/10.3389/fgene.2018.00085},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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.
AU  - Ahmad,H
AU  - Requena,T
AU  - Frejo,L
AU  - Cobo,M
AU  - Gallego-Martinez,A
AU  - Martin,F
AU  - Lopez-Escamez,JA
AU  - Bronstein,AM
DO  - 10.3389/fgene.2018.00085
PY  - 2018///
SN  - 1664-8021
TI  - Clinical and functional characterization of a missense ELF2 variant in a CANVAS Family
T2  - Frontiers in Genetics
UR  - http://dx.doi.org/10.3389/fgene.2018.00085
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000428198000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/69132
VL  - 9
ER  -
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