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Eur J Hum Genet. 2012 Jan;20(1):20-6. doi: 10.1038/ejhg.2011.136. Epub 2011 Aug 3.

Discrepancies in reporting the CAG repeat lengths for Huntington's disease.

Collaborators (549)

Barth K, Correia Guedes L, Maria Finisterra A, Bascuñana Garde M, Bos R, Ecker D, Held C, Koppers K, Laurà M, Martínez Descals A, McLean T, Mestre T, Minster S, Monza D, Townhill J, Orth M, Padieu H, Paterski L, Peppa N, Koivisto SP, Rialland A, Røren N, Šašinková P, Cubillo PT, van Walsem MR, Witjes-Ané MN, Yudina E, Zielonka D, Zielonka E, Zinzi P, Bachoud-Lévi AC, Bentivoglio AR, Biunno I, Bonelli R, Burgunder JM, Dunnett SB, Ferreira JJ, Handley OJ, Heiberg A, Illmann T, Landwehrmeyer GB, Levey J, Nielsen JE, Päivärinta M, Roos RA, Rojo Sebastián A, Tabrizi SJ, Vandenberghe W, Verellen-Dumoulin C, Zaremba J, Uhrova T, Wahlström J, Bonelli RM, Herranhof B, Holl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinger K, Scheibl M, Hecht K, Lilek S, Müller N, Schöggl H, Ullah J, Brugger F, Hepperger C, Hotter A, Mahlknecht P, Nocker M, Seppi K, Wenning G, Buratti L, Hametner EM, Holas C, Hussl A, Mair K, Poewe W, Wolf E, Zangerl A, Braunwarth EM, Ribaï P, Flamez A, Morez V, de Raedt S, Boogaerts A, Vandenberghe W, van Reijen D, Klempíř J, Kucharík M, Roth J, Nielsen JE, Hjermind LE, Jakobsen O, Stokholm J, Hasholt L, Nørremølle A, Sørensen SA, Hiivola H, Martikainen K, Tuuha K, Peippo M, Sipponen M, Kosinski CM, Milkereit E, Probst D, Sass C, Schiefer J, Schlangen C, Werner CJ, Gelderblom H, Priller J, Prüss H, Spruth EJ, Andrich J, Hoffmann R, Kraus PH, Muth S, Prehn C, Saft C, Salmen S, Stamm C, Steiner T, Strassburger K, Lange H, Friedrich A, Hunger U, Löhle M, Schmidt S, Storch A, Wolz A, Wolz M, Lambeck J, Zucker B, Boelmans K, Ganos C, Hidding U, Lewerenz J, Münchau A, Orth M, Schmalfeld J, Stubbe L, Zittel S, Heinicke W, Longinus B, Uni M, Bürk K, Möller JC, Rissling I, Peinemann A, Städtler M, Weindl A, Bechtel N, Beckmann H, Bohlen S, Hölzner E, Lange H, Reilmann R, Rohm S, Rumpf S, Schepers S, Beister A, Dose M, Hammer K, Kieni J, Leythaeuser G, Marquard R, Raab T, Richter S, Selimbegovic-Turkovic A, Schrenk C, Schuierer M, Wiedemann A, Barth K, Buck A, Connemann J, Ecker D, Eschenbach C, Held C, Landwehrmeyer B, Lezius F, Nepper S, Niess A, Orth M, Süssmuth S, Trautmann S, Weydt P, Cormio C, Difruscolo O, Sciruicchio V, Serpino C, de Tommaso M, Capellari S, Cortelli P, Gallassi R, Poda R, Rizzo G, Scaglione C, Bertini E, Ghelli E, Ginestroni A, Massaro F, Mechi C, Paganini M, Piacentini S, Pradella S, Romoli AM, Sorbi S, Abbruzzese G, Bandettini di Poggio M, Di Maria E, Ferrandes G, Mandich P, Marchese R, Albanese A, Di Bella D, Di Donato S, Gellera C, Genitrini S, Mariotti C, Monza D, Nanetti L, Paridi D, Soliveri P, Tomasello C, De Michele G, Di Maio L, Rinaldi C, Valeria Russo C, Salvatore E, Tucci T, Cannella M, Codella V, De Gregorio F, De Nicola N, Martino T, Simonelli M, Squitieri F, Bentivoglio AR, Catalli C, Di Giacopo R, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Modoni A, Piano C, Piccininni C, Quaranta D, Romano S, Soleti F, Spadaro M, Zinzi P, van Hout MS, van Vugt JP, Marit de Weert A, Bolwijn JJ, Dekker M, Leenders KL, van Oostrom JC, Bos R, Dumas EM, Jurgens CK, van den Bogaard SJ, Roos RA, 't Hart EP, Witjes-Ané MN, Kremer B, Verstappen CC, Heiberg A, van Walsem MR, Aaserud O, Wehus R, Bjørgo K, Fannemel M, Gørvell P, Koivisto SP, Retterstøl L, Overland T, Stokke B, Bjørnevoll I, Sando SB, Sitek E, Slawek J, Soltan W, Boczarska-Jedynak M, Jasinska-Myga B, Opala G, Kodowska-Duda G, Banaszkiewicz K, Szczudlik A, Rudziñska M, Wójcik M, Dec M, Krawczyk M, Bryl A, Ciesielska A, Klimberg A, Marcinkowski J, Sempoowicz J, Zielonka D, Samara H, Janik P, Kalbarczyk A, Kwiecinski H, Jamrozik Z, Antczak J, Jachinska K, Rakowicz M, Richter P, Ryglewicz D, Witkowski G, Zdzienicka E, Zaremba J, Suek A, Krysa W, Mestre T, Guedes L, Coelho M, Mendes T, Valadas A, Ferreira JJ, Cavaco S, Damásio J, Magalhães M, Gago M, Garrett C, Guerra MR, Barrero F, Morales B, Cubo E, Mariscal N, Sánchez J, Alonso-Frech F, Rabasa Perez M, Fenollar M, García R, García R, Quiroga PP, Vázquez Rivera S, Villanueva C, Bascuñana M, Fatás Ventura M, García Ribas G, García de Yébenes J, López-Sendón Moreno JL, Cubillo PT, García Ruíz PJ, Martínez-Descals A, José Saiz Artiga M, Sánchez V, Noguera Perea F, Lorenza F, Torres MM, Reinante G, Vivancos Moreau L, Barbera MA, Badenes Guia D, Hernanz LC, Catena JL, Rojo Sebastián A, Ferrer PQ, Tome Carruesco G, Bas J, Busquets N, Calopa M, Dalmau Elorza M, Díez C, López A, Durán S, Terol S, Floriach Robert M, Garzón Ruíz B, González Casado A, Haro Martínez I, Viladrich CM, Pons i Càrdenas R, Roca E, Llesoy JR, Ruiz Idiago JM, Ruíz Vergara M, Soriano García S, Villa Riballo A, Gorospe A, Legarda I, Arques PN, Torres Rodríguez MJ, Vives B, Gaston I, Bosca M, Burguera JA, Garcia AC, Pålhagen SE, Paucar M, Svenningsson P, Walldén Reza-Soltani T, Höglund A, Sandström B, Wahlström J, Høsterey-Ugander U, Fredlund G, Constantinescu R, Neleborn-Lingefjärd L, Tedroff J, Esmaeilzadeh M, Winnberg E, Burgunder JM, Burgunder Y, Stebler Y, Kaelin A, Romero I, Schüpbach M, Zaugg SW, Jack R, Matheson K, Miedzybrodzka Z, Rae D, Simpson S, Summers F, Ure A, Crooks J, Curtis A, de Souza J, Rickards H, Wright J, Barker RA, Di Pietro A, Fisher K, Goodman A, Hill S, Kershaw A, Mason S, Paterson N, Raymond L, Bisson J, Busse M, Clenaghan C, Ellison-Rose L, Handley O, Hunt S, Townhill J, Price K, Rosser A, Edwards M, Hughes T, McGill M, Pearson P, Porteous M, Smith P, Zeman A, Causley A, Harrower T, Howcroft D, Lambord N, Rankin J, Brockie P, Foster J, Johns N, McKenzie S, Rothery J, Thomas G, Yates S, Miller J, Ritchie S, Burrows L, Fletcher A, Harding A, Laver F, Silva M, Thomson A, Barnes K, Chu C, Hobson E, Jamieson S, Markova I, Thomson J, Toscano J, Wild S, Yardumian P, Bourne C, Clayton C, Dipple H, Clapton J, Grant J, Gross D, Hallam C, Middleton J, Murch A, Patino D, Andrews T, Dougherty A, Kavalier F, Golding C, Lashwood A, Robertson D, Ruddy D, Whaite A, Patton M, Peterson M, Rose S, Andrews T, Bruno S, Chu E, Doherty K, Golding C, Henley S, Lahiri N, Novak M, Patel A, Read J, Rosser E, Say M, Tabrizi S, Taylor R, Warner T, Wild E, Arran N, Callaghan J, Craufurd D, Fullam R, Howard L, Huson S, Oughton E, Partington-Jones L, Snowden J, Sollom A, Stopford C, Thompson J, Trender-Gerhad I, Verstraelen N, Westmoreland L, Nemeth AH, Suida G, Harrison D, Hughes M, Parkinson A, Soltysiak B, Bandmann O, Bradbury A, Gill P, Fairtlough H, Fillingham K, Foustanos I, Peppa N, Tidswell K.

Abstract

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

PMID:
21811303
PMCID:
PMC3234505
DOI:
10.1038/ejhg.2011.136
[Indexed for MEDLINE]
Free PMC Article
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