Journal article
Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16
Neurogenetics, Vol.5(2), pp.109-114
06/2004
DOI: 10.1007/s10048-004-0175-2
PMCID: PMC1866166
PMID: 15029481
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
), Δ
2642
(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.
Details
- Title: Subtitle
- Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16
- Creators
- Luc Djoussé - Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USABeth Knowlton - Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, MA 02118, USAMichael R Hayden - Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, CanadaElisabeth W Almqvist - Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, CanadaRyan R Brinkman - Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, CanadaChristopher A Ross - Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USARussel L Margolis - Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USAAdam Rosenblatt - Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USAAlexandra Durr - Hopital de la Salpetriere, Paris, FranceCatherine Dode - Hopital de la Salpetriere, Paris, FrancePatrick J Morrison - Department of Medical Genetics, Belfast City Hospital Trust, Belfast, UKAndrea Novelletto - Department of Cell Biology, University of Calabria, Rende, ItalyMarina Frontali - Institute of Experimental Medicine, CNR, Rome, ItalyRonald J. A Trent - Department of Medicine, University of Sydney, Sydney, AustraliaElizabeth McCusker - Neurology Department, Westmead Hospital, Sydney, AustraliaEstrella Gómez-Tortosa - Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, SpainDavid Mayo Cabrero - Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, SpainRandi Jones - Emory Neurobehavioral Center, Atlanta, Georgia, USAAndrea Zanko - UCSF Division of Medical Genetics, San Francisco, California, USAMartha Nance - Department of Neurology, Hennepin County Medical Center, Minneapolis, Minnesota, USARuth K Abramson - Department of Neuropsychiatry and Behavior, WMS Hall Psychiatric Institute, Columbia, South Carolina, USAOksana Suchowersky - Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaJane S Paulsen - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USAMadaline B Harrison - Department of Neurology, University of Virginia, Charlottesville, Virginia, USAQiong Yang - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USAL. Adrienne Cupples - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USAJayalakshmi Mysore - Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USAJames F Gusella - Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USAMarcy E MacDonald - Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USARichard H Myers - Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA, Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, MA 02118, USA, e-mail
- Resource Type
- Journal article
- Publication Details
- Neurogenetics, Vol.5(2), pp.109-114
- DOI
- 10.1007/s10048-004-0175-2
- PMID
- 15029481
- PMCID
- PMC1866166
- NLM abbreviation
- Neurogenetics
- ISSN
- 1364-6745
- eISSN
- 1364-6753
- Language
- English
- Date published
- 06/2004
- Academic Unit
- Psychiatry; Psychological and Brain Sciences
- Record Identifier
- 9984083825402771
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