Frataxin levels in peripheral tissue in Friedreich ataxia

Annals of Clinical and Translational Neurology
Michael LazaropoulosDavid R Lynch

Abstract

Friedreich ataxia (FRDA) is an autosomal recessive ataxia resulting from mutations in the frataxin gene (FXN). Such mutations, usually expanded guanine-adenine-adenine (GAA) repeats, give rise to decreased levels of frataxin protein in both affected and unaffected tissues. The goal was to understand the relationship of frataxin levels in peripheral tissues to disease status. Frataxin levels were measured in buccal cells and blood, and analyzed in relation to disease features. Site-directed mutant frataxin was also transfected into human embryonic kidney cells to model results from specific point mutations. There was no evidence for change in frataxin levels over time with repeated measures analysis, although linear regression analysis of cross-sectional data predicted a small increase over decades. GAA repeat length predicted frataxin levels in both tissues, and frataxin levels themselves predicted neurological ratings (accounting for age). Compound heterozygous patients for a GAA expansion and a point mutation in FXN generally had lower levels of frataxin than those homozygous for the presence of two GAA repeat expansions, though levels varied dramatically between tissues in some compound heterozygotes for point mutations. The...Continue Reading

References

Aug 13, 1998·Human Molecular Genetics·H KoutnikovaM Koenig
Oct 16, 1999·Archives of Neurology·M Pandolfo
Apr 15, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·M L McCormackD R Lynch
Jul 20, 2000·The Journal of Biological Chemistry·S Dhe-PaganonS E Shoelson
May 22, 2002·Archives of Neurology·David R LynchRobert B Wilson
Jul 12, 2002·Movement Disorders : Official Journal of the Movement Disorder Society·Danqing ZhuGarth A Nicholson
Sep 2, 2004·European Journal of Human Genetics : EJHG·C H ZühlkeE Schwinger
Jan 31, 2007·Annals of Neurology·Irene De BiaseSanjay I Bidichandani
Jan 12, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Lisa S FriedmanDavid R Lynch
Aug 3, 2010·Molecular Genetics and Metabolism·Eric C DeutschDavid R Lynch
Jun 22, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Wolfgang NachbauerSylvia Boesch
Mar 14, 2012·Archives of Neurology·Mathieu AnheimMichel Koenig
Mar 27, 2012·Human Molecular Genetics·Barbara TomassiniRoberto Testi
Jul 4, 2012·Journal of Child Neurology·Sean R RegnerDavid R Lynch
Dec 1, 2012·Journal of Neurology·Francesco SaccàAlessandro Filla
Jul 24, 2013·Journal of Neurochemistry·Pilar González-Cabo, Francesc Palau
Jul 24, 2013·Journal of Neurochemistry·Caterina MariottiSylvia Boesch
Nov 1, 2013·BioMed Research International·Provvidenza Maria AbruzzoRita Casadio
Aug 28, 2014·Annals of Neurology·Elisabetta SoragniJames R Rusche
Oct 23, 2014·Acta Neurologica Scandinavica·L SeyerD R Lynch

❮ Previous
Next ❯

Citations

Feb 10, 2016·Scientific Reports·Santiago E FarajJavier Santos
Dec 5, 2015·Frontiers in Molecular Neuroscience·Nathalie FaggianelliAnnalisa Pastore
Jan 11, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·David R LynchElizabeth Kichula
Jul 18, 2019·Expert Opinion on Pharmacotherapy·Alexandra ClayDavid R Lynch
Jan 13, 2017·Annals of Clinical and Translational Neurology·Sub H Subramony
May 21, 2019·Frontiers in Neuroscience·Sylvia Boesch, Elisabetta Indelicato
Jan 25, 2020·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Parisa AfsharianDavid R Lynch
Aug 16, 2017·Annals of Clinical and Translational Neurology·Elisia ClarkDavid R Lynch
Mar 27, 2019·Annals of Clinical and Translational Neurology·David R LynchJennifer M Farmer
May 10, 2020·Journal of Neurology·Alexandra ClayDavid R Lynch
Apr 26, 2019·Annals of Clinical and Translational Neurology·Elisia ClarkDavid R Lynch
Aug 17, 2019·Frontiers in Cellular Neuroscience·Piergiorgio La RosaFiorella Piemonte
Jan 9, 2021·Molecular and Cellular Neurosciences·Jara Moreno-LoriteJavier Díaz-Nido
Feb 26, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Davide DoniPaola Costantini
May 16, 2021·Molecular & Cellular Proteomics : MCP·Jill S NapieralaMarek Napierala
Jul 9, 2021·Journal of Multidisciplinary Healthcare·David R LynchKimberly Y Lin
Oct 26, 2021·Expert Opinion on Emerging Drugs·Layne N Rodden, David R Lynch

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding
electrophoresis
transfection
biopsies

Related Concepts

Related Feeds

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.