Publications by authors named "Huw R Morris"
Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.
View Article and Find Full Text PDFBackground: Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.
Methods: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results.
Article Synopsis
- Copy Number Variations (CNVs) are crucial in understanding complex diseases and vary across different populations, necessitating large sample studies for accurate analysis.
- The CNV-Finder pipeline utilizes deep learning, specifically Long Short-Term Memory (LSTM) networks, to streamline the identification of CNVs in specific genomic areas, making subsequent analyses like genome sequencing more efficient.
- The tool has been validated with data from various cohorts, focusing on genes related to neurological diseases, and includes an interactive web application for researchers to visualize and refine their findings based on model predictions.
Article Synopsis
- Knowledge of the genetic factors contributing to Parkinson's disease has significantly expanded, starting from the identification of the first mutation in α-synuclein to discovering various other related genes.
- Genetic research helps understand the diverse symptoms of Parkinson's disease and promotes the search for new biomarkers and treatment options, with several clinical trials in progress.
- Efforts to include previously under-represented populations in genetic studies are fostering collaboration and promising new insights, although challenges persist, offering opportunities for a more comprehensive understanding of the disease worldwide.
The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson's disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives.
View Article and Find Full Text PDFPathogenic variants in the gene represent the most common cause of autosomal dominant Parkinson's disease (PD) worldwide. We identified the p.L1795F variant in 14 White/European ancestry PD patients, including two families with multiple affected carriers and seven additional affected individuals with familial PD using genotyping and sequencing data from more than 50,000 individuals through GP2, AMP-PD, PDGENEration, and CENTOGENE.
View Article and Find Full Text PDFAn increasing number of repeat expansion disorders have been found to cause both rare and common neurological disease. This is exemplified in recent discoveries of novel repeat expansions underlying a significant proportion of several late-onset neurodegenerative disorders, such as CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia syndrome) and spinocerebellar ataxia type 27B. Most of the 60 described repeat expansion disorders to date are associated with neurological disease, providing substantial challenges for diagnosis, but also opportunities for management in a clinical neurology setting.
View Article and Find Full Text PDFBackground: Seed amplification assay (SAA) testing has been developed as a biomarker for the diagnosis of α-synuclein-related neurodegenerative disorders.
Objective: The objective of this study was to assess the rate of α-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) and to analyze clinical and pathological features of SAA-positive and -negative cases.
Methods: A total of 96 cerebrospinal fluid samples from clinically diagnosed PSP (n = 59) and CBS (n = 37) cases were analyzed using α-synuclein SAA.
Background: Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.
Objective: We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.
Methods: We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples.
Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.
View Article and Find Full Text PDFEthnic Differences in Atypical Parkinsonism-is South Asian PSP Different?
Mov Disord Clin Pract
November 2024
Article Synopsis
- Progressive supranuclear palsy (PSP) is a debilitating condition that has been under-studied in non-white European populations, prompting an investigation into its characteristics among South Asian patients.
- A study involving 27 South Asian PSP patients (primarily Indians) revealed a mean age of onset at 63.8 years, with a notable 22% experiencing early onset before age 60, and common symptoms including parkinsonism and cognitive dysfunction.
- The findings indicated higher occurrences of atypical symptoms and family history of parkinsonism, suggesting that current MDS diagnostic criteria may not adequately capture the clinical picture in this ethnic group, highlighting the need for further research.
Article Synopsis
- - Up to 80% of patients with Parkinson's disease experience dementia, but the timing varies widely, and the relationship between Parkinson's disease dementia and dementia with Lewy bodies is still debated.
- - A study analyzed genetic data from 7804 patients to investigate how genetic factors influence the development of dementia in Lewy body diseases, revealing certain risk and protective alleles.
- - Key findings include the identification of the risk allele rs429358, which increases the odds of developing dementia, and protective alleles near specific genes that may help prevent it, highlighting the need for further research with confirmed cases.
Article Synopsis
- * A study analyzed 4,685 sporadic FTD cases and found significant genetic variants at the MAPT and APOE loci that increase the risk for the disease, indicating potential genetic overlap with other neurodegenerative diseases.
- * The genetic risk factors appear to vary by population, with MAPT and APOE associations predominantly found in Central/Nordic and Mediterranean Europeans, suggesting a need for further research into these population-specific features for better understanding of sporadic FTD.
Article Synopsis
- * A study involving 6,766 PD patients over several years examined how genetic factors influence motor progression and mortality, revealing the APOE ε4 allele as significantly impacting mortality rates.
- * Four new genetic loci were identified, linked to motor progression, suggesting potential targets for future treatment strategies in PD, although further investigation is necessary to understand their biological implications.
Background And Objectives: Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism.
View Article and Find Full Text PDFArticle Synopsis
- Multiple system atrophy (MSA) is a neurodegenerative disease that leads to symptoms like parkinsonism and ataxia, but its genetic causes are not well understood and treatment options are limited to supportive care.
- A comprehensive study involving the whole genome sequencing of nearly 900 MSA patients and over 7,000 controls discovered four key genetic risk factors associated with the disease.
- The research identified potential susceptibility genes and provided insights into how genetic variations influence gene expression in brain cells, offering a valuable resource for further studies on similar diseases.
Article Synopsis
- Pick's disease is a rare form of frontotemporal dementia characterized by Pick bodies in the brain, which are linked to the MAPT gene and its haplotypes, H1 and H2.
- The study aimed to investigate how the MAPT H2 haplotype influences the risk, age of onset, and duration of Pick's disease.
- Data was collected from 338 individuals with confirmed Pick's disease across multiple sites, and associations of MAPT variants with the disease were analyzed using statistical models.
Background: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.
View Article and Find Full Text PDFBackground: Motor complications are well recognized in Parkinson's disease (PD), but their reported prevalence varies and functional impact has not been well studied.
Objectives: To quantify the presence, severity, impact and associated factors for motor complications in PD.
Methods: Analysis of three large prospective cohort studies of recent-onset PD patients followed for up to 12 years.
Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson's disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype.
View Article and Find Full Text PDFPathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy.
View Article and Find Full Text PDFImportance: The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H1 and H2, various structural forms of 17q21.
View Article and Find Full Text PDFBackground: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) show a high prevalence and rapid progression of dysphagia, which is associated with reduced survival. Despite this, the evidence base for gastrostomy is poor, and the optimal frequency and outcomes of this intervention are not known. We aimed to characterise the prevalence and outcomes of gastrostomy in patients with these three atypical parkinsonian disorders.
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