We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.
We did not find any association between C9orf72 repeat expansion and repeat size with ICH compared with controls or with dementia when assessing ICH patients only.
Patients classified as dALS (having a positive family history of dementia of any type in a 1<sup>st</sup> or 2<sup>nd</sup> degree relative) are eligible for C9orf72 testing only.<b>Results:</b> Currently, 29.5% (34/115) of US NEALS clinics have participated in the program.
In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed next-generation sequencing panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions.
A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia.
Advances in large-scale genetics and genomics have revealed intronic hexanucleotide repeat expansions in the gene encoding C9ORF72 as a main genetic cause of ALS and frontotemporal dementia (FTD), the second most common cause of early-onset dementia after Alzheimer's disease.
The hexanucleotide repeat in the first intron of the C9orf72 gene is the most significant cause of amyotropic lateral sclerosis as well as some forms of fronto-temporal dementia.
Our observation learns that a repeat expansion disorder like C9ORF72 should be considered in patients with a combination of young-onset dementia, psychiatric symptoms and/or photosensitive epilepsy.
In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia.
Amongst the 6 family members analyzed, the p.P392L SQSTM1 mutation segregated as expected with PDB, whereas the C9orf72 expansion segregated with frontal cognitive impairment or dementia in all but one carrier.
In addition, we found that assessing family history for dementia may identify other family members likely to be carrying the C9orf72 expansion, reduce the number of sporadic cases, and thus increase our understanding of disease penetrance.
Among participants in a genetic study of psychoses (N=739), two pairs of related individuals had C9orf72 expansions, of whom three were diagnosed with schizophrenia (SZ) / schizoaffective disorder (SZA), but their clinical features did not suggestdementia or ALS.
In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls.
In this study, DNA from 79 patients with sIBM was collected and the sequencing of 38 genes associated with hereditary inclusion body myopathy (IBM), myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, distal myopathy, amyotrophic lateral sclerosis and dementia along with C9orf72 hexanucleotide repeat analysis was performed.
The phenotypic spectrum of C9ORF72 hexanucleotide repeat expansion mutation has been reported to include parkinsonian syndrome, Huntington's disease-like syndrome and dementia syndrome.
We report detection of the DPR aggregates very early in C9ORF72 FTD development and also describe childhood intellectual disability as a clinical feature preceding dementia.
Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.
We developed gene panel based technologies to assess 16 genes known to harbour mutations causal of dementia and combined these with PCR based assessments of the C9orf72 hexanucleotide repeat expansion and the octapeptide repeat region of PRNP.