Using genomics to solve a 20-year case study
(Children's National Health System) After 20 years, a patient's family learned that their daughter had two rare disorders, Angelman syndrome and P450scc deficiency, which was detected after researchers found out she had uniparental disomy, two copies of chromosome 15 from one parent and none from another. On April 27, the researchers will receive an award at the Pediatric Endocrine Society's Annual Meeting for best novel insight published in Hormone Research in Paediatrics in 2018.
Angelman syndrome (AS) is a neurodegenerative disorder caused by functional loss of the maternal ubiquitin-protein ligase 3A gene. Nonepileptic myoclonus, also described as tremulous movement, often occurs during puberty and increases in adulthood. The involuntary movement in AS has not been defined patho-physiologically and the drugs used such as levetiracetam and piracetam are not always effective. Recently, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, perampanel (PER), was used to alleviate myoclonus in progressive myoclonus epilepsy.
European Journal of Human Genetics, Published online: 09 March 2020; doi:10.1038/s41431-020-0595-yCommon genetic variation in the Angelman syndrome imprinting centre affects the imprinting of chromosome 15
Publication date: Available online 21 February 2020Source: NeuroscienceAuthor(s): Diana C. Rotaru, Edwin J. Mientjes, Ype ElgersmaAbstractThe UBE3A gene is part of the chromosome 15q11-q13 region that is frequently deleted or duplicated, leading to several neurodevelopmental disorders. Angelman syndrome (AS) is caused by the absence of functional maternally derived UBE3A protein, while the paternal UBE3A gene is present but silenced specifically in neurons. Patients with AS present with severe neurodevelopmental delay, with pronounced motor deficits, absence of speech, intellectual disability, epilepsy, and sleep problems....
Publication date: Available online 19 February 2020Source: NeuroscienceAuthor(s): Vishnu Shandilya M C, Akash GautamAbstractActivity-regulated cytoskeleton-associated (Arc) gene is one of the effector neuronal immediate early genes (IEG) that is rapidly upregulated after neuronal activation and is involved in synaptic long-term potentiation and depression. In recent years, it has been implicated in several cognitive disorders, viz. Angelman syndrome, Alzheimer’s disease, fragile-X syndrome, etc. It undergoes quick transcription and highly regulated translation after exposure to a novel environment. Previous studies h...
This study sheds new light on the neuronal functions of UBE3A and offers new prospects for understanding the pathogenesis of UBE3A-related disorders. PMID: 32087286 [PubMed - as supplied by publisher]
Condition: Angelman Syndrome Intervention: Drug: GTX-102 Sponsors: GeneTx Biotherapeuics, LLC.; Ultragenyx Pharmaceutical Inc Not yet recruiting
Journal of Clinical Sleep Medicine, Ahead of Print.
Translational Psychiatry, Published online: 27 January 2020; doi:10.1038/s41398-020-0720-2Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome
ierlorenzo Pallante Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samp...