p62/SQSTM1 analysis in frontotemporal lobar degeneration
Louise Miller1, Sara Rollinson1, Janis Bennion Callister1
1Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
Neurobiology of Aging
|December 1, 2014
Summary
Mutations in the p62/SQSTM1 gene are a rare cause of frontotemporal lobar degeneration (FTLD). This study identified three novel mutations in UK patients, confirming p62/SQSTM1
Area of Science:
- Neurogenetics
- Molecular Biology
- Human Genetics
Background:
- Mutations in the p62/SQSTM1 gene are an infrequent cause of frontotemporal lobar degeneration (FTLD).
- Investigating genetic factors is crucial for understanding FTLD pathogenesis.
Purpose of the Study:
- To determine the prevalence of p62/SQSTM1 mutations in a UK cohort of FTLD patients.
- To identify novel mutations within the p62/SQSTM1 gene associated with FTLD.
Main Methods:
- Sequencing of the entire open reading frame of the p62/SQSTM1 gene.
- Analysis of a large cohort of patients diagnosed with FTLD from the United Kingdom.
- Southern blot analysis for confirmation of repeat expansion mutations in C9orf72.
Main Results:
- Identification of three novel mutations in the p62/SQSTM1 gene in four patients.
- One identified mutation resulted in a premature stop codon, likely impairing protein function.
- A p62/SQSTM1 mutation was found in a patient with a C9orf72 repeat expansion.
Conclusions:
- These findings reinforce the role of p62/SQSTM1 gene mutations as a cause of frontotemporal lobar degeneration.
- The study expands the known genetic landscape of FTLD.
- Further research into p62/SQSTM1's function in neurodegeneration is warranted.
