Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurology. 2012 Mar 6;78(10):690-5. doi: 10.1212/WNL.0b013e318249f683. Epub 2012 Feb 8.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion.

Collaborators (674)

Durr A, Rosenblatt A, Frati L, Perlman S, Conneally PM, Klimek ML, Diggin M, Hadzi T, Duckett A, Ahmed A, Allen P, Ames D, Anderson C, Anderson K, Anderson K, Andrews T, Ashburner J, Axelson E, Aylward E, Barker RA, Barth K, Barton S, Baynes K, Bea A, Beall E, Beg MF, Beglinger LJ, Biglan K, Bjork K, Blanchard S, Bockholt J, Bommu SR, Brossman B, Burrows M, Calhoun V, Carlozzi N, Chesire A, Chiu E, Chua P, Connell RJ, Connor C, Corey-Bloom J, Craufurd D, Cross S, Cysique L, Santos RD, Davis J, Decolongon J, DiPietro A, Doucette N, Downing N, Dudler A, Dunn S, Ecker D, Epping EA, Erickson D, Erwin C, Evans K, Factor SA, Farias S, Fatas M, Fiedorowicz J, Fullam R, Furtado S, Garde MB, Gehl C, Geschwind MD, Goh A, Gooblar J, Goodman A, Griffith J, Groves M, Guttman M, Hamilton J, Harrington D, Harris G, Heaton RK, Helmer K, Henneberry M, Hershey T, Herwig K, Howard E, Hunter C, Jankovic J, Johnson H, Johnson A, Jones K, Juhl A, Kim EY, Kimble M, King P, Klimek ML, Klöppel S, Koenig K, Komiti A, Kumar R, Langbehn D, Leavitt B, Leserman A, Lim K, Lipe H, Lowe M, Magnotta VA, Mallonee WM, Mans N, Marietta J, Marshall F, Martin W, Mason S, Matheson K, Matson W, Mazzoni P, McDowell W, Miedzybrodzka Z, Miller M, Mills J, Miracle D, Montross K, Moore D, Mori S, Moser DJ, Moskowitz C, Newman E, Nopoulos P, Novak M, O'Rourke J, Oakes D, Ondo W, Orth M, Panegyres P, Pease K, Perlman S, Perlmutter J, Peterson A, Phillips M, Pierson R, Potkin S, Preston J, Quaid K, Radtke D, Rae D, Rao S, Raymond L, Reading S, Ready R, Reece C, Reilmann R, Reynolds N, Richardson K, Rickards H, Ro E, Robinson R, Rodnitzky R, Rogers B, Rosenblatt A, Rosser E, Rosser A, Price K, Price K, Ryan P, Salmon D, Samii A, Schumacher J, Schumacher J, Sendon JL, Shear P, Sheinberg A, Shpritz B, Siedlecki K, Simpson SA, Singer A, Smith J, Smith M, Smith G, Snyder P, Song A, Sran S, Stephan K, Stober J, Sümuth S, Suter G, Tabrizi S, Tempkin T, Testa C, Thompson S, Thomsen T, Thumma K, Toga A, Trautmann S, Tremont G, Tupper D, Turner J, Uc E, Vaccarino A, van Duijn E, Van Walsem M, Vik S, Vonsattel JP, Vuletich E, Warner T, Wasserman P, Wassink T, Waterman E, Weaver K, Weir D, Welsh C, Werling-Witkoske C, Wesson M, Westervelt H, Weydt P, Wheelock V, Williams K, Williams J, Wodarski M, Wojcieszek J, Wood J, Wood-Siverio C, Wu S, Yastrubetskaya O, de Yebenes JG, Zhao YQ, Zimbelman J, Zschiegner R, Aaserud O, Abbruzzese G, Andrews T, Andrich J, Antczak J, Arran N, Artiga MJ, Bachoud-Lévi A, Banaszkiewicz K, di Poggio MB, Bandmann O, Barbera MA, Barker RA, Barrero F, Barth K, Bas J, Beister A, Bentivoglio AR, Bertini E, Biunno I, Bjørgo K, Bjørnevoll I, Bohlen S, Bonelli RM, Bos R, Bourne C, Bradbury A, Brockie P, Brown F, Bruno S, Bryl A, Buck A, Burg S, Burgunder JM, Burns P, Burrows L, Busquets N, Busse M, Calopa M, Carruesco GT, Casado AG, Catena JL, Chu C, Ciesielska A, Clapton J, Clayton C, Clenaghan C, Coelho M, Connemann J, Craufurd D, Crooks J, Cubillo PT, Cubo E, Curtis A, De Michele G, De Nicola A, de Souza J, de Weert A, de Yébenes JG, Dekker M, Descals A, Di Maio L, Di Pietro A, Dipple H, Dose M, Dumas EM, Dunnett S, Ecker D, Elifani F, Ellison-Rose L, Elorza MD, Eschenbach C, Evans C, Fairtlough H, Fannemel M, Fasano A, Fenollar M, Ferrandes G, Ferreira JJ, Fillingham K, Finisterra AM, Fisher K, Fletcher A, Foster J, Foustanos I, Frech FA, Fullam R, Fullham R, Gago M, García RG, García SS, Garrett C, Gellera C, Gill P, Ginestroni A, Golding C, Goodman A, Gørvell P, Grant J, Griguoli A, Gross D, Guedes L, BascuñanaGuerra M, Guerra MR, Guerrero R, Guia DB, Guidubaldi A, Hallam C, Hamer S, Hammer K, Handley OJ, Harding A, Hasholt L, Hedge R, Heiberg A, Heinicke W, Held C, Hernanz LC, Herranhof B, Herrera CD, Hidding U, Hiivola H, Hill S, Hjermind LE, Hobson E, Hoffmann R, Holl AH, Howard L, Hunt S, Huson S, Ialongo T, Idiago JM, Illmann T, Jachinska K, Jacopini G, Jakobsen O, Jamieson S, Jamrozik Z, Janik P, Johns N, Jones L, Jones U, Jurgens CK, Kaelin A, Kalbarczyk A, Kershaw A, Khalil H, Kieni J, Klimberg A, Koivisto SP, Koppers K, Kosinski CM, Krawczyk M, Kremer B, Krysa W, Kwiecinski H, Lahiri N, Lambeck J, Lange H, Laver F, Leenders KL, Levey J, Leythaeuser G, Lezius F, Llesoy JR, Löhle M, López CD, Lorenza F, Loria G, Magnet M, Mandich P, Marchese R, Marcinkowski J, Mariotti C, Mariscal N, Markova I, Marquard R, Martikainen K, Martínez IH, Martínez-Descals A, Martino T, Mason S, McKenzie S, Mechi C, Mendes T, Mestre T, Middleton J, Milkereit E, Miller J, Miller J, Minster S, Möller JC, Monza D, Morales B, Moreau LV, Moreno JL, Münchau A, Murch A, Nielsen JE, Niess A, Nørremølle A, Novak M, O'Donovan K, Orth M, Otti D, Owen M, Padieu H, Paganini M, Painold A, Päivärinta M, Partington-Jones L, Paterski L, Paterson N, Patino D, Patton M, Peinemann A, Peppa N, Perea MF, Peterson M, Piacentini S, Piano C, Pons i Càrdenas R, Prehn C, Price K, Probst D, Quarrell O, Quiroga PP, Raab T, Rakowicz M, Raman A, Raymond L, Reilmann R, Reinante G, Reisinger K, Retterstøl L, Ribaï P, Riballo AV, Ribas GG, Richter S, Rickards H, Rinaldi C, Rissling I, Ritchie S, Rivera SV, Robert MF, Roca E, Romano S, Romoli AM, Roos RA, Røren N, Rose S, Rosser E, Rosser A, Rossi F, Rothery J, Rudzinska M, Ruíz PJ, Ruíz BG, Russo CV, Ryglewicz D, Saft C, Salvatore E, Sánchez V, Sando SB, Šašinková P, Sass C, Scheibl M, Schiefer J, Schlangen C, Schmidt S, Schöggl H, Schrenk C, Schüpbach M, Schuierer M, Sebastián AR, Selimbegovic-Turkovic A, Sempolowicz J, Silva M, Sitek E, Slawek J, Snowden J, Soleti F, Soliveri P, Sollom A, Soltan W, Sorbi S, Sørensen SA, Spadaro M, Städtler M, Stamm C, Steiner T, Stokholm J, Stokke B, Stopford C, Storch A, Straßburger K, Stubbe L, Sulek A, Szczudlik A, Tabrizi S, Taylor R, Terol SD, Thomas G, Thompson J, Thomson A, Tidswell K, Torres MM, Toscano J, Townhill J, Trautmann S, Tucci T, Tuuha K, Uhrova T, Valadas A, van Hout MS, van Oostrom JC, van Vugt JP, van Walsem MR, Vandenberghe W, Verellen-Dumoulin C, Vergara MR, Verstappen CC, Verstraelen N, Viladrich CM, Villanueva C, Wahlström J, Warner T, Wehus R, Weindl A, Werner CJ, Westmoreland L, Weydt P, Wiedemann A, Wild E, Wild S, Witjes-Ané MN, Witkowski G, Wójcik M, Wolz M, Wolz A, Wright J, Yardumian P, Yates S, Yudina E, Zaremba J, Zaugg SW, Zdzienicka E, Zielonka D, Zielonka E, Zinzi P, Zittel S, Zucker B, Adams J, Agarwal P, Antonijevic I, Beck C, Chiu E, Churchyard A, Colcher A, Corey-Bloom J, Dorsey R, Drazinic C, Dubinsky R, Duff K, Factor S, Foroud T, Furtado S, Giuliano J, Greenamyre T, Higgins D, Jankovic J, Jennings D, Kang UJ, Kostyk S, Kumar R, Leavitt B, LeDoux M, Mallonee W, Marshall F, Mohlo E, Morgan J, Oakes D, Panegyres P, Panisset M, Perlman S, Perlmutter J, Quaid K, Raymond L, Revilla F, Robertson S, Robottom B, Sanchez-Ramos J, Scott B, Shannon K, Shoulson I, Singer C, Tabbal S, Testa C, van Kammen D, Vetter L, Walker F, Warner J, Weiner W, Wheelock V, Yastrubetskaya O, Barton S, Broyles J, Clouse R, Coleman A, Davis R, Decolongon J, DeLaRosa J, Deuel L, Dietrich S, Dubinsky H, Eaton K, Erickson D, Fitzpatrick MJ, Frucht S, Gartner M, Goldstein J, Griffith J, Hickey C, Hunt V, Jaglin J, Klimek ML, Lindsay P, Louis E, Loy C, Lucarelli N, Malarick K, Martin A, McInnis R, Moskowitz C, Muratori L, Nucifora F, O'Neill C, Palao A, Peavy G, Quesada M, Schmidt A, Segro V, Sperin E, Suter G, Tanev K, Tempkin T, Thiede C, Wasserman P, Welsh C, Wesson M, Zauber E.

Author information

  • 1Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.

Abstract

OBJECTIVE:

Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs.

METHODS:

We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression.

RESULTS:

An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele.

CONCLUSIONS:

Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors.

Comment in

PMID:
22323755
[PubMed - indexed for MEDLINE]
PMCID:
PMC3306163
Free PMC Article

Images from this publication.See all images (1)Free text

Figure 1
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk