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Single haplotype located on chromosome 9 being associated with both ALS and FTD

The authors, Peter Heutink & John van Swieten, on their publications that appeared this week ahead of print back to back in Neuron and in the Neurobiology of Aging

Renton et al., A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS- FTD, Neuron (2011), doi:10.1016/j.neuron.2011.09.010

DeJesus-Hernandez et al., Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS, Neuron (2011), doi:10.1016/j.neuron.2011.09.011

"The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALSFTD) locus contains one of the last major unidentified autosomal dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype is present in cases linked to this region and that this risk haplotype is associated with one third of familial ALS in the Finnish population. 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 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."

See also: related news item on vumc.nl