Journal ArticleDOI
A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.
Reads0
Chats0
TLDR
A parametric survival model based on CAG repeat length is developed to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients using the largest cohort of HD patients analyzed to date.Abstract:
Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.read more
Citations
More filters
Journal ArticleDOI
Within-Subject Template Estimation for Unbiased Longitudinal Image Analysis
TL;DR: This paper introduces a novel longitudinal image processing framework, based on unbiased, robust, within-subject template creation, for automatic surface reconstruction and segmentation of brain MRI of arbitrarily many time points and successfully reduces variability and avoids over-regularization.
Journal ArticleDOI
Huntington's disease: from molecular pathogenesis to clinical treatment
TL;DR: Predictive genetic testing and findings of neuroimaging studies show that Huntington's disease is emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset.
Journal ArticleDOI
Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data.
Sarah J. Tabrizi,Douglas R. Langbehn,Blair R. Leavitt,Raymund A.C. Roos,Alexandra Durr,David Craufurd,Christopher Kennard,Stephen Hicks,Nick C. Fox,Rachael I. Scahill,Beth Borowsky,Allan J. Tobin,H. Diana Rosas,Hans J. Johnson,Ralf Reilmann,Bernhard Landwehrmeyer,Julie C. Stout,Julie C. Stout +17 more
TL;DR: The feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study is shown, providing evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls.
Journal ArticleDOI
Huntington disease: natural history, biomarkers and prospects for therapeutics
Christopher A. Ross,Elizabeth Aylward,Edward J. Wild,Douglas R. Langbehn,Jeffrey D. Long,John H. Warner,Rachael I. Scahill,Blair R. Leavitt,Julie C. Stout,Jane S. Paulsen,R Reilmann,Paul G. Unschuld,Alice Wexler,Russell L. Margolis,Sarah J. Tabrizi +14 more
TL;DR: The natural history of HD is described, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features, and potential future roles of these biomarkers in clinical trials are reviewed.
Journal ArticleDOI
Detection of Huntington’s disease decades before diagnosis: The Predict HD study
Jane S. Paulsen,Douglas R. Langbehn,Julie C. Stout,Elizabeth Aylward,Christopher A. Ross,Martha Nance,Mark Guttman,Shannon A. Johnson,Marcy E. MacDonald,Leigh J. Beglinger,Kevin Duff,Elise Kayson,Kevin M. Biglan,Ira Shoulson,David Oakes,Michael R. Hayden +15 more
TL;DR: The findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.
References
More filters
Journal ArticleDOI
The Statistical Analysis of Failure Time Data.
Journal ArticleDOI
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
Marcy E. MacDonald,Christine Ambrose,Mabel P. Duyao,Richard H. Myers,Carol Lin,Lakshmi Srinidhi,Glenn Barnes,Sherryl A.M. Taylor,Marianne James,Nicolet Groot,Heather MacFarlane,Barbara Jenkins,Mary Anne Anderson,Nancy S. Wexler,James F. Gusella,Gillian P. Bates,Sarah Baxendale,Holger Hummerich,Susan F. Kirby,Mike North,S. Youngman,Richard Mott,Günther Zehetner,Zdenek Sedlacek,Annemarie Poustka,Anna-Maria Frischauf,Hans Lehrach,Alan Buckler,Deanna M. Church,Lynn Doucette-Stamm,Michael Conlon O'Donovan,Laura Riba-Ramirez,Manish A. Shah,Vincent P. Stanton,Scott A. Strobel,Karen M. Draths,Jennifer L. Wales,Peter B. Dervan,David E. Housman,Michael R. Altherr,Rita Shiang,Leslie M. Thompson,Thomas J. Fielder,John J. Wasmuth,Danilo A. Tagle,John Valdes,Lawrence W. Elmer,Marc W. Allard,Lucio H. Castilla,Manju Swaroop,Kris Blanchard,Francis S. Collins,Russell G. Snell,Tracey Holloway,Kathleen Gillespie,Nicole A. Datson,Duncan Shaw,Peter S. Harper +57 more
TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.
Journal Article
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more
TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Book
Analysis of Survival Data
David Cox,D. Oakes +1 more
TL;DR: In this article, the authors give a concise account of the analysis of survival data, focusing on new theory on the relationship between survival factors and identified explanatory variables and conclude with bibliographic notes and further results that can be used for student exercises.
Journal ArticleDOI
The Statistical Analysis of Failure Time Data
TL;DR: This book complements the other references well, and merits a place on the bookshelf of anyone concerned with the analysis of lifetime data from any eld.
Related Papers (5)
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
Marcy E. MacDonald,Christine Ambrose,Mabel P. Duyao,Richard H. Myers,Carol Lin,Lakshmi Srinidhi,Glenn Barnes,Sherryl A.M. Taylor,Marianne James,Nicolet Groot,Heather MacFarlane,Barbara Jenkins,Mary Anne Anderson,Nancy S. Wexler,James F. Gusella,Gillian P. Bates,Sarah Baxendale,Holger Hummerich,Susan F. Kirby,Mike North,S. Youngman,Richard Mott,Günther Zehetner,Zdenek Sedlacek,Annemarie Poustka,Anna-Maria Frischauf,Hans Lehrach,Alan Buckler,Deanna M. Church,Lynn Doucette-Stamm,Michael Conlon O'Donovan,Laura Riba-Ramirez,Manish A. Shah,Vincent P. Stanton,Scott A. Strobel,Karen M. Draths,Jennifer L. Wales,Peter B. Dervan,David E. Housman,Michael R. Altherr,Rita Shiang,Leslie M. Thompson,Thomas J. Fielder,John J. Wasmuth,Danilo A. Tagle,John Valdes,Lawrence W. Elmer,Marc W. Allard,Lucio H. Castilla,Manju Swaroop,Kris Blanchard,Francis S. Collins,Russell G. Snell,Tracey Holloway,Kathleen Gillespie,Nicole A. Datson,Duncan Shaw,Peter S. Harper +57 more
Unified huntington’s disease rating scale: Reliability and consistency
Karl Kieburtz,John B. Penney,Peter Corno,Neal G. Ranen,Ira Shoulson,Andrew Feigin,Davi Abwender,J. Timothy Greenarnyre,Donald S. Higgins,Frederick J. Marshall,Joshua L. Goldstein,Kimberly Steinberg,Charles Shih,Irene H. Richard,Charlyne Hickey,Carol Zimmerman,Constance Orme,Kathy Claude,David Oakes,Daniel S. Sax,Anthony Kim,Steven M. Hersch,Randi Jones,Alexander P. Auchus,David B. Olsen,Cheryl Bissey-Black,Allen Rubin,Rose Schwartz,Richard Dubinsky,William Mallonee,Carolyn Gray,Nan Godfrey,Greg Suter,Kathleen M. Shannon,Glenn T. Stebbins,Jean A. Jaglin,Karen Marder,Stuart Taylor,Elan D. Louis,Carol Moskowitz,Deborah Zeck Thorne,Naomi Zubin,Nancy S. Wexler,Michael R. Swenson,Jane S. Paulsen,Neal R. Swerdlow,Roger L. Albin,Christine Wernette,Francis O. Walker,Vicki Hunt +49 more
Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data.
Sarah J. Tabrizi,Douglas R. Langbehn,Blair R. Leavitt,Raymund A.C. Roos,Alexandra Durr,David Craufurd,Christopher Kennard,Stephen Hicks,Nick C. Fox,Rachael I. Scahill,Beth Borowsky,Allan J. Tobin,H. Diana Rosas,Hans J. Johnson,Ralf Reilmann,Bernhard Landwehrmeyer,Julie C. Stout,Julie C. Stout +17 more
Detection of Huntington’s disease decades before diagnosis: The Predict HD study
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more