HFE p.C282Y heterozygosity is associated with earlier disease onset in Friedreich ataxia. Issue 7 (3rd January 2014)

• Record Type: Journal Article
• Authors: Delatycki, Martin B.; Tai, Geneieve; Corben, Louise; Yiu, Eppie M.; Evans‐Galea, Marguerite V.; Stephenson, Sarah E.M.; Gurrin, Lyle; Allen, Katrina J.; Lynch, David; Lockhart, Paul J.
• Is Part Of: Movement disorders. Volume 29:Issue 7(2014)
• Page Start: 940
• Page End: 943
• Publication Date: 2014-01-03
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.25795
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mds25795-sec-0001" sec-type="section"> <title>Background</title> <p>Friedreich ataxia (FRDA) generally results from reduced frataxin, a mitochondrial protein involved in iron metabolism. We assessed whether HFE p.C282Y and/or p.H63D heterozygosity modifies age at disease onset or disease severity in individuals with FRDA.</p> </sec> <sec id="mds25795-sec-0002" sec-type="section"> <title>Methods</title> <p>One hundred seventy individuals with FRDA were assessed for the association of HFE p.C282Y and p.H63D with (1) age at disease onset and (2) Friedreich Ataxia Rating Scale (FARS) score.</p> </sec> <sec id="mds25795-sec-0003" sec-type="section"> <title>Results</title> <p>After adjusting for the smaller <italic>FXN</italic> GAA repeat size and sex, individuals with FRDA and heterozygous for p.C282Y had disease onset on average 3.72 years earlier than those homozygous for the wild‐type amino acid (<italic>P</italic> = 0.02). Neither mutation affected disease severity as measured by FARS.</p> </sec> <sec id="mds25795-sec-0004" sec-type="section"> <title>Conclusions</title> <p>It is hypothesized that the association between p.C282Y heterozygosity and an earlier age at FRDA onset relates to exacerbation of the already dysregulated iron metabolism that plays a major role in the pathogenesis of FRDA. © 2014 International Parkinson and Movement Disorder Society</p> </sec> </abstract>