Apart from concluding that the clinical features of this mutation are compatible with AD, we identified ring-formed Aβ plaques but did not further study the overall neuropathology.
Therefore, one possible distinguishing feature of this mutation is that the mutant NC1 domains do not fold or function properly and thus, the mutant proteins do not participate in heterotrimer formation.
Because studies of chromosome 9p-linked families and several C9orf72 cohort descriptions [ 4, 5, 7, 12- 15, 20] suggested that psychosis (as defined by the presence of delusions or hallucinations of any type) might be a distinguishing feature of this mutation, data on psychotic symptoms will be presented separately; other symptoms will be discussed based on timing.
The other 9 cancers each featured 1 mutation.
Since the discovery of chromosome 9 open reading frame 72 (C9orf72) hexanucleotide expansions as a cause of FTD and ALS, research groups and consortia around the world have reported their respective observations of the clinical features associated with this mutation.
The first studies to describe the phenotype associated with C9orf72 expansions at a group level therefore sought to characterize the neuropsychiatric features associated with this mutation.
To prevent such misinterpretation due to the unnoticed presence of the Crb1 rd8/rd8 mutation in the future, we here aim to evaluate the range and variability of phenotypic features associated with this mutation.
Thalamic and cerebellar atrophy have been reported in mutation carriers [ 5, 6], and Mahoney and colleagues hypothesized that thalamic and cerebellar projections could be related to the neuropsychiatric features associated with this mutation, including hallucinations and/or delusions [ 6].
We reviewed the recent literature on C9orf72-associated FTD and ALS with focus on the neuropsychiatric features associated with this mutation, as well as the experience at University of California, San Francisco.
Given that C9ORF72 expansion likely represents the most common genetic cause for FTD/ALS, many clinicians seek to identify features specific to this mutation to assist in the anticipation of disease onset in families and assessment of disease severity in patients.
