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.
|Titolo:||A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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|Neuron 2011 - Renton - c9orf72 gene.pdf||Post-print||NON PUBBLICO - Accesso privato/ristretto||Administrator Richiedi una copia|
|A Hexanucleotide Repeat Expansion in C9ORF72.pdf||PDF editoriale||NON PUBBLICO - Accesso privato/ristretto||Administrator Richiedi una copia|