Monday, 17 October 2011

A hexanucleotide expansion on #9p21 causes ALS-FTD

Level 3: For those of you who missed Huw Morris' presentation at the ABN in Newcastle.

Epub ahead of printRenton et al. A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD. Neuron. 2011 Sep 21.

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. The investigators 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 they 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.

"This will almost certainly be the neurology paper of the year. The finding will now allow pre-symptomatic diagnosis, the creation of new animal models and hopefully new insights into MND-ALS-FTD that will ultimately lead to a treatment."

Extra-curricular reading for Medical Students: MND, FTD

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