Affiliations: [a] Fondazione IRCCS Ca’ Granda, Ospedale Policlinico, Milan, Italy
| [b] Dino Ferrari Center, University of Milan, Milan, Italy
Correspondence:
[*]
Correspondence to: Maria Serpente, Fondazione IRCCs Ca’Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122, Milan, Italy. Tel.: +39 0255023858; Fax: +39 02 55036580; E-mails: maria.serpente@unimi.it; maria.serpente@policlinico.mi.it
Abstract: Background:C9orf72 hexanucleotide GGGGCC (G4C2) large repeat expansions within the first intron of the gene are a major cause of familial frontotemporal dementia, but also of apparently sporadic cases. Alleles with > 30 repeats are often considered pathogenic, but the repeat length threshold is still undefined. It is also unclear if C9orf72 intermediate alleles (9–30 repeats) have clinically significant effects. Objectives:We correlated the presence of C9orf72 intermediate alleles with clinical diagnoses in a perspective cohort referred to a secondary memory clinic. Methods:All samples were genotyped with AmplideXPCR/CE C9ORF72 Kit (Asuragen, Inc), an optimized C9orf72 PCR amplification reagent. Results:We showed that in patients with Alzheimer’s disease (AD) the frequency of the intermediate repeat alleles was significantly increased versus controls (34/54, 63%AD versus 16/39, 41%CTRLs, *p = 0.01, OR 2.91 CI 95%1.230–6.077), whereas no significant differences (p > 0.05) were observed when comparing all other dementias with non-demented individuals. Conclusion:Our findings suggest that C9orf72 intermediate repeat units may represent a genetic risk factor, contributing to the occurrence of AD. Nevertheless, further longitudinal studies, including larger cohort of subjects with intermediate alleles with long-term follow-up, would be needed to confirm these results.
