Genome-wide association studies have identified as a Parkinson's disease (PD) risk locus, with a common missense variant p.Asp543Asn in the synaptic vesicle glycoprotein 2C (SV2C) protein significantly associated with PD. We examined if other rare variants also influence PD risk. We analyzed sequencing data of 9810 East Asian individuals comprising 4298 patients and 5512 controls and identified 55 rare nonsynonymous variants. There was no significant association of rare nonsynonymous or loss-of-function variants with PD. Our findings show that besides p.Asp543Asn, other rare coding variants in do not play a major role in PD susceptibility in East Asia.
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http://dx.doi.org/10.1177/1877718X241300298 | DOI Listing |
F1000Res
March 2025
The Gertrude H. Sergievsky Center College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, 10032, USA.
Next-generation sequencing (NGS) has enabled analysis of rare and uncommon variants in large study cohorts. A common strategy to overcome these low frequencies and/or small effect sizes relies on collapsing strategies, i.e.
View Article and Find Full Text PDFJ Cancer Policy
March 2025
Department of Social Medicine and Public Health, Faculty of Public Health, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; Institute for Rare Diseases, 4023 Plovdiv, Bulgaria. Electronic address:
Rare cancers, defined by an annual incidence of fewer than 6 per 100,000 cases, pose significant challenges due to their complexity, lack of expertise, and limited treatment options. In Bulgaria, these challenges are compounded by limited resources, fragmented care, and outdated policies. This study investigates policy stakeholder perspectives to identify gaps and propose policy alternatives for rare cancer care in Bulgaria, with implications for the broader European Union (EU) context.
View Article and Find Full Text PDFAm J Hum Genet
March 2025
Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, Institut Imagine, Université Paris Cité, Paris, France. Electronic address:
The Mediator complex regulates protein-coding gene transcription by coordinating the interaction of upstream enhancers with the basal transcription machinery at the promoter. Pathogenic variants in Mediator subunits typically lead to neurodevelopmental or neurodegenerative disorders with variable clinical presentations, designated as MEDopathies. Here, we report the identification of 25 individuals from 18 families with bi-allelic MED16 variants who have a multiple congenital anomalies (MCAs)-intellectual disability syndrome.
View Article and Find Full Text PDFJIMD Rep
March 2025
Biomedical and Molecular Metabolism Research, Faculty of Natural and Agricultural Sciences, North-West University Potchefstroom South Africa.
Primary trimethylaminuria (TMAU) is characterized by systemic accumulation of trimethylamine (TMA) due to the deficient activity of flavin-containing monooxygenase 3 (FMO3). The disorder does not have detrimental pathophysiological consequences, but patients develop psychological symptoms due to the emotionally debilitating bodily odor defined as decaying fish that affects their quality of life. Here, we illustrate the utility of a diagnostic workup on an adolescent with primary TMAU, including biochemical and genetic investigations that confirm the diagnosis.
View Article and Find Full Text PDFMaterials (Basel)
February 2025
Département des Sciences Appliquées, Université du Québec a Chicoutimi, Saguenay, QC G7H 2B1, Canada.
Application of rare earths (RE) as grain refiners is well-known in the technology of aluminum alloys for the automotive industry. In the current study, Al-2.4%Cu-0.
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