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

  • Luc Djoussé
  • Beth Knowlton
  • Michael R. Hayden
  • Elisabeth W. Almqvist
  • Ryan R. Brinkman
  • Christopher A. Ross
  • Russel L. Margolis
  • Adam Rosenblatt
  • Alexandra Durr
  • Catherine Dode
  • Patrick J. Morrison
  • Andrea Novelletto
  • Marina Frontali
  • Ronald J. A. Trent
  • Elizabeth McCusker
  • Estrella Gómez-Tortosa
  • David Mayo Cabrero
  • Randi Jones
  • Andrea Zanko
  • Martha Nance
  • Ruth K. Abramson
  • Oksana Suchowersky
  • Jane S. Paulsen
  • Madaline B. Harrison
  • Qiong Yang
  • L. Adrienne Cupples
  • Jayalakshmi Mysore
  • James F. Gusella
  • Marcy E. MacDonald
  • Richard H. Myers
Original Article
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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 disease Modifier Onset age Genetics Trinucleotide repeat HD gene 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Luc Djoussé
    • 1
  • Beth Knowlton
    • 2
  • Michael R. Hayden
    • 3
  • Elisabeth W. Almqvist
    • 3
  • Ryan R. Brinkman
    • 3
  • Christopher A. Ross
    • 4
  • Russel L. Margolis
    • 4
  • Adam Rosenblatt
    • 4
  • Alexandra Durr
    • 5
  • Catherine Dode
    • 5
  • Patrick J. Morrison
    • 6
  • Andrea Novelletto
    • 7
  • Marina Frontali
    • 8
  • Ronald J. A. Trent
    • 9
  • Elizabeth McCusker
    • 10
  • Estrella Gómez-Tortosa
    • 11
  • David Mayo Cabrero
    • 11
  • Randi Jones
    • 12
  • Andrea Zanko
    • 13
  • Martha Nance
    • 14
  • Ruth K. Abramson
    • 15
  • Oksana Suchowersky
    • 16
  • Jane S. Paulsen
    • 17
  • Madaline B. Harrison
    • 18
  • Qiong Yang
    • 19
  • L. Adrienne Cupples
    • 19
  • Jayalakshmi Mysore
    • 20
  • James F. Gusella
    • 20
  • Marcy E. MacDonald
    • 20
  • Richard H. Myers
    • 1
    • 2
  1. 1.Evans Department of Medicine, Section of Preventive Medicine and EpidemiologyBoston University School of MedicineBostonUSA
  2. 2.Department of NeurologyBoston University School of MedicineBostonUSA
  3. 3.Center for Molecular Medicine and TherapeuticsUniversity of British ColumbiaVancouverCanada
  4. 4.Department of PsychiatryJohns Hopkins UniversityBaltimoreUSA
  5. 5.Hopital de la SalpetriereParisFrance
  6. 6.Department of Medical GeneticsBelfast City Hospital TrustBelfastUK
  7. 7.Department of Cell BiologyUniversity of CalabriaRendeItaly
  8. 8.Institute of Experimental Medicine, CNRRomeItaly
  9. 9.Department of MedicineUniversity of SydneySydneyAustralia
  10. 10.Neurology DepartmentWestmead HospitalSydneyAustralia
  11. 11.Servicio de Neurología y GenéticaFundación Jiménez DíazMadridSpain
  12. 12.Emory Neurobehavioral CenterAtlantaUSA
  13. 13.UCSF Division of Medical GeneticsSan FranciscoUSA
  14. 14.Department of NeurologyHennepin County Medical CenterMinneapolisUSA
  15. 15.Department of Neuropsychiatry and BehaviorWMS Hall Psychiatric InstituteColumbiaUSA
  16. 16.Department of Clinical NeurosciencesUniversity of CalgaryCalgaryCanada
  17. 17.Department of PsychiatryUniversity of IowaIowa CityUSA
  18. 18.Department of NeurologyUniversity of VirginiaCharlottesvilleUSA
  19. 19.Department of BiostatisticsBoston University School of Public HealthBostonUSA
  20. 20.Molecular Neurogenetics Unit, Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA

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