scholarly journals Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase

2004 ◽  
Vol 36 (11) ◽  
pp. 1225-1229 ◽  
Author(s):  
Michael A Simpson ◽  
Harold Cross ◽  
Christos Proukakis ◽  
David A Priestman ◽  
David C A Neville ◽  
...  
Keyword(s):  
Epilepsy Syndrome ◽  
Loss Of Function ◽  
Gm3 Synthase ◽  
Symptomatic Epilepsy

Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA

2020 ◽  
Author(s):  
Hessa S. Alsaif ◽  
Heba Youssef E. L. Khashab ◽  
Fowzan S. Alkuraya
Keyword(s):  
Epilepsy Syndrome ◽  
Symptomatic Epilepsy

scholarly journals Risk factors influencing the outcomes in infants with epilepsy

2007 ◽  
Vol 47 (5) ◽  
pp. 202 ◽  
Author(s):  
Setyo Handryastuti ◽  
Irawan Mangunatmadja
Keyword(s):  
Risk Factors ◽  
Age Of Onset ◽  
Age At Onset ◽  
Epileptic Seizures ◽  
Neonatal Seizure ◽  
Epilepsy Syndrome ◽  
Developmental Status ◽  
Factors Influencing ◽  
History Of ◽  
Symptomatic Epilepsy

Background Epilepsy in young children should always beconsidered as a symptom of an underlying brain disease. Parentsand caregivers often asked whether the seizures can be controlledand whether the epilepsy will affect the child development.Objective To find out risk factors influencing the outcomes ininfants with epilepsy.Methods This was a retrospective study on infants aged 1 monthuntil 12 months with recurrent epileptic seizures. We looked forthe risk factors as sex, types of medication, age at onset of seizure,epilepsy syndrome, etiology of epilepsy, history of neonatal seizure,first EEG features, and type of seizure for the last 6 month-period.The outcomes evaluated were controlled seizure and developmentalstatus.Results Hundred forty infants with epilepsy were reviewed,consisted of 84 (60%) infants with symptomatic epilepsy, and 56(40%) infants categorized as idiopathic. Forty-six (33%) infantshad controlled seizure, while 94 (67%) infants had uncontrolledseizure. Abnormal developmental status was found in 75 infants(54%). Abnormal developmental status was more found in infantswith polytherapy, age at onset of 1-4 months, symptomaticepilepsy, positive remote symptomatic, history of neonatal seizure,abnormality of first EEG, and uncontrolled seizure. Uncontrolledseizure of epilepsy was more found in infants with polytherapy,early age at onset (1-4 month old), symptomatic epilepsy, positiveremote symptomatic, history of neonatal seizure, and abnormalityof first EEG.Conclusion Our data indicate that classifying syndrome of epilepsythrough diagnostic screening and age of onset are important todetermine the outcomes.

scholarly journals Network for Therapy in Rare Epilepsies (NETRE): Lessons From the Past 15 Years

2021 ◽  
Vol 11 ◽  
Author(s):  
Celina von Stülpnagel ◽  
Andreas van Baalen ◽  
Ingo Borggraefe ◽  
Kirsten Eschermann ◽  
Till Hartlieb ◽  
...  
Keyword(s):  
Data Entry ◽  
International Exchange ◽  
Epilepsy Syndrome ◽  
Channel Blockers ◽  
Loss Of Function ◽  
Mri Findings ◽  
Data Entry Form ◽  
Epileptic Disorder ◽  
Starting Point ◽  
Vanishing Twin Syndrome

Background: In 2005, Network for Therapy in Rare Epilepsies (NETRE)—was initiated in order to share treatment experiences among clinicians in patients with rare epilepsies. Here we describe the structure of the rapidly growing NETRE and summarize some of the findings of the last 15 years.Methodology/Structure of NETRE: NETRE is organized in distinct groups (currently >270). Starting point is always a patient with a rare epilepsy/ epileptic disorder. This creates a new group, and next, a medical coordinator is appointed. The exchange of experiences is established using a data entry form, which the coordinator sends to colleagues. The primary aim is to exchange experiences (retrospectively, anonymously, MRI results also non-anonymously) of the epilepsy treatment as well as on clinical presentation and comorbidities NETRE is neither financed nor sponsored.Results: Some of the relevant results: (1) first description of FIRES as a new epilepsy syndrome and its further investigation, (2) in SCN2A, the assignment to gain- vs. loss-of-function mutations has a major impact on clinical decisions to use or avoid treatment with sodium channel blockers, (3) the important aspect of avoiding overtreatment in CDKL5 patients, due to loss of effects of anticonvulsants after 12 months, (4) pathognomonic MRI findings in FOXG1 patients, (5) the first description of pathognomonic chewing-induced seizures in SYNGAP1 patients, and the therapeutic effect of statins as anticonvulsant in these patients, (6) the phenomenon of another reflex epilepsy—bathing epilepsy associated with a SYN1 mutation. Of special interest is also a NETRE group following twins with genetic and/or structural epilepsies [including vanishing-twin-syndrome and twin-twin-transfusion syndrome) [= “Early Neuroimpaired Twin Entity” (ENITE)].Discussion and Perspective: NETRE enables clinicians to quickly exchange information on therapeutic experiences in rare diseases with colleagues at an international level. For both parents and clinicians/scientist this international exchange is both reassuring and helpful. In collaboration with other groups, personalized therapeutic approaches are sought, but the present limitations of currently available therapies are also highlighted. Presently, the PATRE Project (PATient based phenotyping and evaluation of therapy for Rare Epilepsies) is commencing, in which information on therapies will be obtained directly from patients and their caregivers.

scholarly journals A Rat Model of a Focal Mosaic Expression of PCDH19 Replicates Human Brain Developmental Abnormalities and Behaviors

2020 ◽  
Author(s):  
Andrzej W Cwetsch ◽  
Roberto Narducci ◽  
Maria Bolla ◽  
Bruno Pinto ◽  
Laura Perlini ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Epileptic Encephalopathy ◽  
Epilepsy Syndrome ◽  
Loss Of Function ◽  
Protein Loss ◽  
Proper Understanding ◽  
Developmental Abnormalities ◽  
Mosaic Expression ◽  
Mutant Cells ◽  
The Brain

AbstractPCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9) is an infantile onset epilepsy syndrome characterized by psychiatric (including autistic) sensory and cognitive impairment of varying degrees. EIEE9 is caused by X-linked PCDH19 protein loss of function. Due to random X-chromosome inactivation, EIEE9-affected females present a mosaic population of healthy and Pcdh19-mutant cells. Unfortunately, no mouse models recapitulate to date both the brain histological and behavioural deficits present in people with EIEE9. Thus, the search for a proper understanding of the disease, and possible future treatment is hampered. By inducing a focal mosaicism of Pcdh19 expression using in utero electroporation in rat, we found here that Pcdh19 signaling in specific brain areas is implicated in neuronal migration, as well as in core behaviors related to autism and cognitive function.

Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Mio Aerden ◽  
Lore Vallaeys ◽  
Maureen Holvoet ◽  
Liesbeth De Waele ◽  
Kris Van Den Bogaert ◽  
...  
Keyword(s):  
Epilepsy Syndrome ◽  
Symptomatic Epilepsy

Whole exome sequencing identifies the firstSTRADApoint mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE)

2016 ◽  
Vol 170 (8) ◽  
pp. 2181-2185 ◽  
Author(s):  
Weimin Bi ◽  
Ian A. Glass ◽  
Donna M. Muzny ◽  
Richard A. Gibbs ◽  
Christine M. Eng ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epilepsy Syndrome ◽  
Whole Exome ◽  
Symptomatic Epilepsy

E3 ubiquitin ligases

2005 ◽  
Vol 41 ◽  
pp. 15-30 ◽  
Author(s):  
Helen C. Ardley ◽  
Philip A. Robinson
Keyword(s):  
Protein Complexes ◽  
Loss Of Function ◽  
Direct Role ◽  
Cellular Processes ◽  
Substrate Protein ◽  
Protein Ubiquitination ◽  
C Terminus ◽  
Full Complement ◽  
Spatio Temporal ◽  
Eukaryotic Organisms

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

Metallic prions

2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown
Keyword(s):  
Prion Protein ◽  
Binding Capacity ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Published Data ◽  
Normal Brain ◽  
Copper Binding ◽  
Loss Of Function ◽  
Spongiform Encephalopathies ◽  
The Brain

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.

Errata

2008 ◽  
Vol 13 (2) ◽  
pp. 5-5
Keyword(s):  
Psychotic Disorders ◽  
Pain Syndrome ◽  
Vestibular Disorders ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Neurologic Disorders ◽  
Upper And Lower Extremities ◽  
Impairment Ratings ◽  
Extensive List ◽  
Mental And Behavioral Disorders

Abstract Although most chapters in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, instruct evaluators to perform impairment ratings by first assigning a diagnosis-based class and then assigning a grade within that class, Chapter 13, The Central and Peripheral Nervous System, continues to use a methodology similar to that of the fifth edition. The latter was criticized for duplicating materials that were presented in other chapters and for producing different ratings, so the revision of Chapter 13 attempts to maintain consistency between this chapter and those that address mental and behavioral disorders, loss of function in upper and lower extremities, loss of bowel control, and bladder and sexual function. A table titled Summary of Chapters Used to Rate Various Neurologic Disorders directs physicians to the relevant chapters (ie, instead of Chapter 13) to consult in rating neurologic disorders; the extensive list of conditions that should be addressed in other chapters includes but is not limited to radiculopathy, plexus injuries and other plexopathies, focal neuropathy, complex regional pain syndrome, visual and vestibular disorders, and a range of primary mood, anxiety, and psychotic disorders. The article comments in detail on sections of this chapter, identifies changes in the sixth edition, and provide guidance regarding use of the new edition, resulting in less duplication and greater consistency.

Impairment Tutorial: Rating Facial Disfigurement After an Injury

1998 ◽  
Vol 3 (4) ◽  
pp. 6-6
Author(s):  
Marc T. Taylor
Keyword(s):  
Current Work ◽  
Workers Compensation ◽  
Loss Of Function ◽  
Facial Disfigurement ◽  
Work Related ◽  
Work Related Injury ◽  
Compensation Claim ◽  
Impairment Ratings

Abstract This article discusses two important cases that involve the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides). First, in Vargas v Industrial Com’n of Arizona, a claimant had a pre-existing non–work-related injury to his right knee as well as a work-related injury, and the issue was apportionment of the pre-existing injury. The court held that, under Arizona's statute, the impairment from the pre-existing injury should be subtracted from the current work-related impairment. In the second case, Colorado courts addressed the issue of apportionment in a workers’ compensation claim in which the pre-existing injury was asymptomatic at the time of the work-related injury (Askey v Industrial Claim Appeals Office). In this case, the court held that the worker's benefits should not be reduced to account for an asymptomatic pre-existing condition that could not be rated accurately using the AMA Guides. The AMA Guides bases impairment ratings on anatomic or physiologic loss of function, and if an examinee presents with two or more sequential injuries and calculable impairments, the AMA Guides can be used to apportion between pre-existing and subsequent impairments. Courts often use the AMA Guides to decide statutorily determined benefits and are subject to interpretation by courts and administrative bodies whose interpretations may vary from state to state.

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