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Introduction
Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative clinical syndrome characterised by insidious behavioural and personality changes. One lingering challenge to bvFTD diagnostic criteria 1 is that some patients meeting criteria present with a slowly progressive course (bvFTD-SP) and plateau at mild symptom severity. 2 These patients have been referred to as bvFTD 'phenocopies' because, although their behavioural features resemble bvFTD, they do not display typical patterns of brain atrophy or hypometabolism at baseline, 3 4 nor do they show progressive volume loss typical of bvFTD, leading some authors to suggest that the syndrome is not caused by a neurodegenerative disease. 1 5 6 The few individuals who have been examined with brain autopsy did not show FTLD pathology, 1 and because these patients often have normal life spans, 1 large pathological series are not available, leaving the neuropathological correlates of bvFTD-SP unclear.
Despite estimates from one group that 'phenocopies' may account for one-third of patients with bvFTD, 2 there has yet to be a study linking bvFTD-SP to a known FTD associated mutation. Recently, a hexanucleotide expansion in chromosome 9 open reading frame 72 (C9ORF72 ) was shown to be the most common genetic abnormality in both familial and sporadic bvFTD and amyotrophic lateral sclerosis (ALS), with bvFTD being the major phenotype in carriers with a dementia syndrome. 7 8 All patients examined displayed frontotemporal lobar degeneration with TDP-43 positive inclusions (FTLD-TDP) pathology. 9 10 Here we report two patients who were diagnosed with bvFTD-SP at the University of California, San Francisco (UCSF) and had C9ORF72 expansions. The presence of the C9ORF72 (C9FTD/ALS) mutation in these patients suggests that some patients with bvFTD-SP may have slowly progressive FTD with pathological inclusions containing TDP-43, the protein associated with bvFTD and ALS in C9ORF72 mutation carriers. 7 8
Methods
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Three hundred and eighty-four patients with FTD clinical spectrum diagnoses and possible or probable Alzheimer's disease (AD) diagnoses (National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorder Association research criteria) were tested for C9ORF72 expansion ( figure 1 ). Eighty-seven patients had a diagnosis of bvFTD (n=61) or FTD-ALS (n=26). Twenty-three (bvFTD=13; FTD-ALS=10) of the 87 patients carried the mutation (C9+). No patient with a non-bvFTD clinical syndrome was C9+....