rare disease
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Epigenetic rewiring in Schinzel-Giedion syndrome
During life, a variety of specialized cells arise to grant the right and timely corrected functions of tissues and organs. Regulation of chromatin in defining specialized genomic regions (e.g. enhancers) plays a key role in developmental transitions from progenitors into cell lineages. These enhancers, properly topologically positioned in 3D space, ultimately guide the transcriptional programs. It is becoming clear that several pathologies converge in differential enhancer usage with respect to physiological situations. However, why some regulatory regions are physiologically preferred, while some others can emerge in certain conditions, including other fate decisions or diseases, remains obscure. Schinzel-Giedion syndrome (SGS) is a rare disease with symptoms such as severe developmental delay, congenital malformations, progressive brain atrophy, intractable seizures, and infantile death. SGS is caused by mutations in the SETBP1 gene that results in its accumulation further leading to the downstream accumulation of SET. The oncoprotein SET has been found as part of the histone chaperone complex INHAT that blocks the activity of histone acetyltransferases suggesting that SGS may (i) represent a natural model of alternative chromatin regulation and (ii) offer chances to study downstream (mal)adaptive mechanisms. I will present our work on the characterization of SGS in appropriate experimental models including iPSC-derived cultures and mouse.
Expanding the role of MAST kinases in brain development and epilepsy: identification of de novo pathogenic variants in MAST4
Developmental disorders of presynaptic vesicle cycling - Synaptotagmin-1 and beyond
Post-diagnostic research on rare genetic developmental disorders presents new opportunities (and a few challenges) for discovery neuroscience and translation. In this talk, Kate will describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence pre-synaptic vesicle cycling (SVC disorders). She will focus on Synaptotagmin-1 Associated Neurodevelopmental Disorder (also known as Baker Gordon Syndrome), first described in 2015 and now diagnosed in more than 50 children and young people worldwide. She will then present work-in-progress by her group on the neurodevelopmental spectrum of SVC disorders more broadly, and discuss opportunities for collaborative neuroscience which can bridge the gaps between genetic cause and complex neurological, cognitive and mental health outcomes.
Improving care for rare disease patients in Europe - Rare Disease Day 2021
Rare Disease Natural History Studies: Experience from the GNAO1 Natural History study in a pre and postpandemic world
Lysosomal storage disorders and their unanticipated links to rare and common diseases
Lysosomal storage diseases are a group of over 70 inherited metabolic disorders, many of which have a neurodegenerative clinical course. Treatments have been developed for a subset of these disorders and are now in routine clinical use. We have found that some neurological and neurodegenerative diseases share unanticipated links to lysosomal storage diseases providing insights into disease pathogenesis. These links also suggest treatments developed for lysosomal disorders may have unanticipated utility in other rare and common diseases.
Treatment of spasticity in HSP and leukodystrophies
Hereditary Spastic Paraplegia (HSP): clinical disease course
How can we develop and implement evidence based rehabilitation in rare disorders?
A challenge in neurogenetics: Huntington disease in kids
How to assess and manage spastic gait in rare diseases?
Semantic variant of primary progressive aphasia, clinical manifestation and underlying neuropathology
Leveraging technology to improve access to rare disease research
rare disease coverage
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