Publications by authors named "J A Winkelmann"
Aims: The Cardiac Conduction System (CCS) is progressively specified during development by interactions among a discrete number of Transcriptions Factors that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain transcription factors (TFs) with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity, however the basis for these alterations has not been established.
View Article and Find Full Text PDFArticle Synopsis
- MEIS1 and MEIS2 are important genes that code for proteins involved in development across various tissues, particularly in the brain, but their specific roles in early neural differentiation need further investigation.
- Research involving knockout and overexpression of these genes in human neural stem cells reveals that MEIS1 and MEIS2 regulate different groups of target genes linked to various biological functions.
- MEIS1 is not only connected to gene regulation, especially in relation to other transcription factors, but it also has a significant risk factor for restless legs syndrome (RLS), as it controls genes associated with this condition.
Background: Exome sequencing has been established as a fundamental tool in genetic diagnostics. It may also provide information about variants in genes unrelated to the primary purpose, so-called secondary findings. Especially, diagnoses of unnoticed inborn cardiac diseases are of high clinical relevance due to therapeutic options in context of prevention of sudden cardiac death.
View Article and Find Full Text PDFTremor-Dominant Movement Disorder in Associated KBG Syndrome.
Tremor Other Hyperkinet Mov (N Y)
September 2024
Article Synopsis
- * A case study of a 24-year-old patient revealed they had a significant tremor disorder, including various types of tremors and additional symptoms like muscle stiffness and coordination issues, alongside some developmental delays and epilepsy.
- * This case underscores the importance of recognizing movement disorders in KBG syndrome, suggesting that genetic testing for pathogenic variants should be considered when diagnosing tremor-related conditions.
Article Synopsis
- - This study examines the link between rare variants in the cullin-3 ubiquitin ligase (CUL3) gene and neurodevelopmental disorders (NDDs), gathering data from multiple centers to explore genetic mutations and their clinical impacts.
- - Researchers identified 37 individuals with CUL3 variants, most of which result in loss-of-function (LoF), leading to intellectual disabilities and possibly autistic traits; specific mechanisms affecting protein stability were also investigated.
- - The findings enhance the understanding of NDDs associated with CUL3 mutations, suggesting that LoF variants are the main cause, which could help inform future diagnostics and treatment strategies.