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Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72
- Source :
- Brain; Vol 135
- Publication Year :
- 2012
-
Abstract
- Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized. We report the clinical and pathological phenotypes associated with pathogenic C9ORF72 mutations in a cohort of 563 cases from Northern England, including 63 with a family history of amyotrophic lateral sclerosis. One hundred and fifty-eight cases from the cohort (21 familial, 137 sporadic) were post-mortem brain and spinal cord donors. We screened DNA for the C9ORF72 mutation, reviewed clinical case histories and undertook pathological evaluation of brain and spinal cord. Control DNA samples (n = 361) from the same population were also screened. The C9ORF72 intronic expansion was present in 62 cases [11% of the cohort; 27/63 (43%) familial, 35/500 (7%) cases with sporadic amyotrophic lateral sclerosis/motor neuron disease]. Disease duration was significantly shorter in cases with C9ORF72-related amyotrophic lateral sclerosis (30.5 months) compared with non-C9ORF72 amyotrophic lateral sclerosis/motor neuron disease (36.3 months, P
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
Population
Real-Time Polymerase Chain Reaction
Cohort Studies
03 medical and health sciences
0302 clinical medicine
C9orf72
medicine
Dementia
Humans
Amyotrophic lateral sclerosis
Age of Onset
education
030304 developmental biology
Aged
Biological Specimen Banks
Inclusion Bodies
Neurons
0303 health sciences
education.field_of_study
DNA Repeat Expansion
C9orf72 Protein
business.industry
Neurodegeneration
Amyotrophic Lateral Sclerosis
Brain
Proteins
DNA
Original Articles
Motor neuron
Middle Aged
medicine.disease
Immunohistochemistry
3. Good health
medicine.anatomical_structure
Phenotype
England
Spinal Cord
Dentate Gyrus
Female
Neurology (clinical)
business
Cognition Disorders
030217 neurology & neurosurgery
Frontotemporal dementia
Subjects
Details
- ISSN :
- 14602156
- Volume :
- 135
- Issue :
- Pt 3
- Database :
- OpenAIRE
- Journal :
- Brain : a journal of neurology
- Accession number :
- edsair.doi.dedup.....fbbe92a9c69e5bca7bd8b2083e24a4aa