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

Authors :
Quarrell, Ow
Handley, O
O'Donovan, K
Dumoulin, C
Ramos Arroyo, M
Biunno, I
Bauer, P
Kline, M
Landwehrmeyer, Gb
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
Bonelli, R
Burgunder, Jm
Dunnett, Sb
Ferreira, Jj
Handley, Oj
Heiberg, A
Illmann, T
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
van Reijen, D
Klempíř, J
Kucharík, M
Roth, J
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
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
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
Buck, A
Connemann, J
Eschenbach, C
Landwehrmeyer, B
Lezius, F
Nepper, S
Niess, A
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
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
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, Silvia
Soleti, F
Spadaro, M
van Hout MS
van Vugt JP
Marit de Weert, A
Bolwijn, Jj
Dekker, M
Leenders, Kl
van Oostrom JC
Dumas, Em
Jurgens, Ck
van den Bogaard SJ
't Hart EP
Kremer, B
Verstappen, Cc
Aaserud, O
Wehus, R
Bjørgo, K
Fannemel, M
Gørvell, P
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
Samara, H
Janik, P
Kalbarczyk, A
Kwiecinski, H
Jamrozik, Z
Antczak, J
Jachinska, K
Rakowicz, M
Richter, P
Ryglewicz, D
Witkowski, G
Zdzienicka, E
Suek, A
Krysa, W
Guedes, L
Coelho, M
Mendes, T
Valadas, A
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
Quiroga, Pp
Vázquez Rivera, S
Villanueva, C
Bascuñana, M
Fatás Ventura, M
García Ribas, G
García de Yébenes, J
López Sendón Moreno JL
García Ruíz PJ
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
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
Càrdenas R, Pons i.
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
Høsterey Ugander, U
Fredlund, G
Constantinescu, R
Neleborn Lingefjärd, L
Tedroff, J
Esmaeilzadeh, M
Winnberg, E
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
Hunt, S
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
Bruno, S
Chu, E
Doherty, K
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
Tidswell, K.
Kaelin, André
Quarrel O.W.
Handley O.
O'Donovan K.
Dumoulin C.
Ramos-Arroyo M.
Biunno I.
Bauer P.
Kline M.
Capellari S.
Cortelli P.
Gallassi R.
Landwehrmeyer G.B.
European Huntington's Disease Network.
Neurology
Clinical sciences
Neuroprotection & Neuromodulation
Quarrell, Ow
Handley, O
O'Donovan, K
Dumoulin, C
Ramos Arroyo, M
Biunno, I
Bauer, P
Kline, M
Landwehrmeyer, Gb
European Huntington's Disease, Network
European Huntington's Disease, N. e. t. w. o. r. k.
Rinaldi, Carlo
Salvatore, Elena
DE MICHELE, Giuseppe
Source :
European Journal of Human Genetics, Vol. 20, No 1 (2012) pp. 20-6
Publication Year :
2012

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.

Details

Language :
English
ISSN :
10184813
Database :
OpenAIRE
Journal :
European Journal of Human Genetics, Vol. 20, No 1 (2012) pp. 20-6
Accession number :
edsair.doi.dedup.....889bb5ecc56cde789666947b81c117e5