A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD

Renton, Ae; Majounie, E; Waite, A; Simón Sánchez, J; Rollinson, S; Gibbs, Jr; Schymick, Jc; Laaksovirta, H; van Swieten JC,; Myllykangas, L; Kalimo, H; Paetau, A; Abramzon, Y; Remes, Am; Kaganovich, A; Scholz, Sw; Duckworth, J; Ding, J; Harmer, Dw; Hernandez, Dg; Johnson, Jo; Mok, K; Ryten, M; Trabzuni, D; Guerreiro, Rj; Orrell, Rw; Neal, J; Murray, A; Pearson, J; Jansen, Ie; Sondervan, D; Seelaar, H; Blake, D; Young, K; Halliwell, N; Callister, Jb; Toulson, G; Richardson, A; Gerhard, A; Snowden, J; Mann, D; Neary, D; Nalls, Ma; Peuralinna, T; Jansson, L; Isoviita, Vm; Kaivorinne, Al; Hölttä Vuori, M; Ikonen, E; Sulkava, R; Benatar, M; Wuu, J; Chiò, A; Restagno, G; Borghero, G; Sabatelli, M; The ITALSGEN Consortium,; Simone, Isabella Laura; Heckerman, D; Rogaeva, E; Zinman, L; Rothstein, Jd; Sendtner, M; Drepper, C; Eichler, Ee; Alkan, C; Abdullaev, Z; Pack, Sd; Dutra, A; Pak, E; Hardy, J; Singleton, A; Williams, Nm; Heutink, P; Pickering Brown, S; Morris, Hr; Tienari, Pj; Traynor, Bj

doi:10.1016/j.neuron.2011.09.010

The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.

Scheda prodotto non validato

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Titolo:	A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD
Autori:	Renton AE Majounie E Waite A Simón Sánchez J Rollinson S Gibbs JR Schymick JC Laaksovirta H van Swieten JC Myllykangas L Kalimo H Paetau A Abramzon Y Remes AM Kaganovich A Scholz SW Duckworth J Ding J Harmer DW Hernandez DG Johnson JO Mok K Ryten M Trabzuni D Guerreiro RJ Orrell RW Neal J Murray A Pearson J Jansen IE Sondervan D Seelaar H Blake D Young K Halliwell N Callister JB Toulson G Richardson A Gerhard A Snowden J Mann D Neary D Nalls MA Peuralinna T Jansson L Isoviita VM Kaivorinne AL Hölttä Vuori M Ikonen E Sulkava R Benatar M Wuu J Chiò A Restagno G Borghero G Sabatelli M The ITALSGEN Consortium SIMONE, Isabella Laura Heckerman D Rogaeva E Zinman L Rothstein JD Sendtner M Drepper C Eichler EE Alkan C Abdullaev Z Pack SD Dutra A Pak E Hardy J Singleton A Williams NM Heutink P Pickering Brown S Morris HR Tienari PJ Traynor BJ mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2011
Rivista:	NEURON
Abstract:	The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.
Handle:	http://hdl.handle.net/11586/87103
Appare nelle tipologie:	1.1 Articolo in rivista

File in questo prodotto:

Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

CINECA IRIS Institutional Research Information System

Scheda prodotto non validato

File in questo prodotto: