Neurogenetics

, Volume 5, Issue 2, pp 109–114

Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

Authors

  • Luc Djoussé
    • Evans Department of Medicine, Section of Preventive Medicine and EpidemiologyBoston University School of Medicine
  • Beth Knowlton
    • Department of NeurologyBoston University School of Medicine
  • Michael R. Hayden
    • Center for Molecular Medicine and TherapeuticsUniversity of British Columbia
  • Elisabeth W. Almqvist
    • Center for Molecular Medicine and TherapeuticsUniversity of British Columbia
  • Ryan R. Brinkman
    • Center for Molecular Medicine and TherapeuticsUniversity of British Columbia
  • Christopher A. Ross
    • Department of PsychiatryJohns Hopkins University
  • Russel L. Margolis
    • Department of PsychiatryJohns Hopkins University
  • Adam Rosenblatt
    • Department of PsychiatryJohns Hopkins University
  • Alexandra Durr
    • Hopital de la Salpetriere
  • Catherine Dode
    • Hopital de la Salpetriere
  • Patrick J. Morrison
    • Department of Medical GeneticsBelfast City Hospital Trust
  • Andrea Novelletto
    • Department of Cell BiologyUniversity of Calabria
  • Marina Frontali
    • Institute of Experimental Medicine, CNR
  • Ronald J. A. Trent
    • Department of MedicineUniversity of Sydney
  • Elizabeth McCusker
    • Neurology DepartmentWestmead Hospital
  • Estrella Gómez-Tortosa
    • Servicio de Neurología y GenéticaFundación Jiménez Díaz
  • David Mayo Cabrero
    • Servicio de Neurología y GenéticaFundación Jiménez Díaz
  • Randi Jones
    • Emory Neurobehavioral Center
  • Andrea Zanko
    • UCSF Division of Medical Genetics
  • Martha Nance
    • Department of NeurologyHennepin County Medical Center
  • Ruth K. Abramson
    • Department of Neuropsychiatry and BehaviorWMS Hall Psychiatric Institute
  • Oksana Suchowersky
    • Department of Clinical NeurosciencesUniversity of Calgary
  • Jane S. Paulsen
    • Department of PsychiatryUniversity of Iowa
  • Madaline B. Harrison
    • Department of NeurologyUniversity of Virginia
  • Qiong Yang
    • Department of BiostatisticsBoston University School of Public Health
  • L. Adrienne Cupples
    • Department of BiostatisticsBoston University School of Public Health
  • Jayalakshmi Mysore
    • Molecular Neurogenetics Unit, Center for Human Genetic ResearchMassachusetts General Hospital
  • James F. Gusella
    • Molecular Neurogenetics Unit, Center for Human Genetic ResearchMassachusetts General Hospital
  • Marcy E. MacDonald
    • Molecular Neurogenetics Unit, Center for Human Genetic ResearchMassachusetts General Hospital
    • Evans Department of Medicine, Section of Preventive Medicine and EpidemiologyBoston University School of Medicine
    • Department of NeurologyBoston University School of Medicine
Original Article

DOI: 10.1007/s10048-004-0175-2

Cite this article as:
Djoussé, L., Knowlton, B., Hayden, M.R. et al. Neurogenetics (2004) 5: 109. doi:10.1007/s10048-004-0175-2

Abstract.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Δ2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Δ2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.

Keywords

Huntington diseaseModifierOnset ageGeneticsTrinucleotide repeatHD gene

Copyright information

© Springer-Verlag 2004