Publications by authors named "A Puschmann"
Variants in GBA1 are important genetic risk factors in Parkinson's disease (PD). GBA1 T369M has been linked to an ∼80 % increased PD risk but the reports are conflicting and the relevance of GBA1 variants in different populations varies. A lack of association between T369M and PD in the Swedish population was recently reported but needs further validation.
View Article and Find Full Text PDFBackground: An increasing number of monogenic conditions underlying stroke are being identified. We explored the possibilities of increasing the diagnostic yield of monogenic stroke in a population under 56 years of age.
Methods: Fifty probands ≤55 years at their first stroke episode were characterized clinically and investigated by whole genome sequencing.
Article Synopsis
- Mutations in the PRKN gene are a leading cause of early-onset Parkinson disease, with the p.R275W variant being the most common among patients.
- Research using patient fibroblasts, isogenic neurons, and human brain samples reveals that the p.R275W mutation significantly reduces PRKN protein levels, impairing mitophagy and mitochondrial degradation.
- Structural simulations indicate that this mutation destabilizes the PRKN protein, leading to a loss-of-function under normal biological conditions.
Article Synopsis
- The study explores how copy number variations (CNVs) affect the development of Parkinson's disease (PD), aiming to identify new genetic mechanisms linked to sporadic cases of the disease.
- Utilizing data from over 11,000 PD patients and nearly 9,000 controls, the researchers discovered 14 significant CNV loci associated with PD, including various gene duplications and deletions.
- The research highlights a higher prevalence of CNVs in specific PD-related genes among patients and suggests that certain CNVs, especially those involving the gene, may lead to earlier onset of the disease in early-onset PD cases.