تجزیه و تحلیل از تکرار hexanucleotide در C9ORF72 در بیماری آلزایمر

Frontotemporal lobar degeneration (FTLD) is a highly familial neurodegenerative disease. It has recently been shown that the most common genetic cause of FTLD and amyotrophic lateral sclerosis (ALS) is a hexanucleotide repeat expansion in C9ORF72. To investigate whether this expansion was specific to the FTLD/ALS disease spectrum, we genotyped the hexanucleotide repeat region of C9ORF72 in a large cohort of patients with Alzheimer's disease (AD). A normal range of repeats was found in all cases. We conclude that the hexanucleotide repeat expansion is specific to the FTLD/ALS disease spectrum.

Frontotemporal lobar degeneration (FTLD) is an umbrella term used to cover the clinical syndromes of frontotemporal dementia, progressive nonfluent aphasia (PNFA), and semantic dementia. In some cases, amyotrophic lateral sclerosis (ALS) is seen in conjunction with FTLD in the same patient. Recently it has been shown that approximately 7% of all cases of FTLD/ALS are caused by a massive expansion of a hexanucleotide (GGGGCC) repeat region in the uncharacterized gene C9ORF72 on chromosome 9p21 ( Dejesus-Hernandez et al., 2011 and Renton et al., 2011). Impairment of memory is not a common (early) symptom of FTLD; however, cases of amnesic FTLD do occur, and these can be misdiagnosed as Alzheimer's disease (AD) ( Graham et al., 2005). Moreover, patients with linguistic forms of AD (logopenic AD) can be misdiagnosed as PNFA, and vice versa ( Hu et al., 2010). Therefore, to investigate whether cryptic cases of FTLD presenting with symptoms of AD can occur, we genotyped the expansion in a large cohort of patients who had been diagnosed by their treating physician with AD, and who fulfilled clinical criteria for AD ( McKhann et al., 1984).