HFE p.C282Y heterozygosity is associated with earlier disease onset in Friedreich ataxia
Related Experiment Video
Updated: May 4, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Martin B Delatycki1, Geneieve Tai, Louise Corben
1Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia; School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia.
Background:
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.
Methods:
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.
Results:
After adjusting for the smaller FXN 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 (P = 0.02). Neither mutation affected disease severity as measured by FARS.
Conclusions:
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.
More Related Videos
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Related Concept Videos
01:21Huntington Disease l: Introduction
01:49Hardy-Weinberg Principle
01:11Genetic Lingo
01:35Pedigree Analysis
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...