A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

作者：Renton Alan E; Majounie Elisa; Waite Adrian; Simon Sanchez Javier; Rollinson Sara; Gibbs J Raphael; Schymick Jennifer C; Laaksovirta Hannu; van Swieten John C; Myllykangas Liisa; Kalimo Hannu; Paetau Anders; Abramzon Yevgeniya; Remes Anne M; Kaganovich Alice; Scholz Sonja W; Duckworth Jamie; Ding Jinhui; Harmer Daniel W; Hernandez Dena G; Johnson Janel O; Mok Kin; Ryten Mina; Trabzuni Danyah; Guerreiro Rita J; Orrell Richard W; Neal James; Murray Alex

来源：Neuron, 2011, 72(2): 257-268.

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.

• 出版日期2011-10-20
• 单位河北医科大学; Microsoft