|
Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a fairly common form of idiopathic generalized epilepsy, representing 5-10% of all epilepsies. This disorder typically first manifests itself between the ages of 12 and 18 with myoclonus occurring early in the morning. Most patients also have tonic-clonic seizures and many also have absence seizures. Linkage studies have demonstrated at least 6 loci for JME, 4 with known causative genes. Most of these genes are ion channels with the one non-ion channel gene having been shown to affect ion channel currents. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ...
The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ...
// G00-G99 - Diseases of the nervous system (G00-G09) Inflammatory diseases of the central nervous system (G00) Bacterial meningitis, not elsewhere classified (G01) Meningitis in bacterial diseases classified elsewhere (G02) Meningitis in other infectious and parasitic diseases classified elsewhere (G03) Meningitis due to other and unspecified causes (G04) Encephalitis, myelitis...
The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ...
The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ...
The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ...
The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ...
eMedicine is an online clinical medical knowledge base that was founded in 1996. ...
Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ...
Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. ...
Tonic-clonic seizures (also known as Grand Mal Seizures, though this term is now discouraged and rarely used in a clinical setting) are a type of generalised seizure affecting the whole brain. ...
Absence seizures are one of several kinds of seizures. ...
Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ...
Signs and symptoms Signs of JME are myoclonus occurring early in the morning. This rarely results in patients falling, but rather dropping objects. Attacks of myoclonia is more common in the arms than the legs. Other seizure types such as generalized tonic-clonic and absence seizures can also occur. Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. ...
The numerous epileptic seizure types are most commonly defined and grouped according to a scheme proposed by the International League Against Epilepsy (ILAE) in 1981. ...
Pathophysiology
CACNB4 CACNB4 encodes a calcium channel β subunit. β subunits are important regulators of calcium channel current amplitude, voltage dependence, and also regulate channel trafficking. The β4 isoform encoded by CACNB4 is most prevalent in the cerebellum. In mice, a naturally occurring null mutation leads to the "lethargic" phenotype, which is similar to JME. There are at least two mutations in the β4 subunit associated with JME, C104F and R482X. When wild-type α1A and β4 subunits are expressed in oocytes they produce large Ba2+ currents that inactivate slowly. Interestingly, incorporation of either of the mutant β4 subunit into channels instead of wild-type subunits produces currents that are larger by 30-40%. The R482X mutation also increases the rate of fast inactivation of the channel. Since these effects are subtle, it is believed that they are contributory rather than completely causative for JME.[1] Ion channels are present in the membranes that surround all biological cells. ...
Ion channels are present in the membranes that surround all biological cells. ...
The cerebellum (Latin: little brain) is a region of the brain that plays an important role in the integration of sensory perception and motor control. ...
An oocyte or ovocyte is a female gametocyte that divides twice by mitosis and meiosis into two other oocytes or into two ootids. ...
For other uses, see Barium (disambiguation). ...
GABRA1 GABRA1 encodes an α subunit of the GABA A receptor, which encodes one of the major inhibitory neurotransmitter receptors. There is one known mutation in this gene that is associated with JME, A322D, which is located in the third segment of the protein. Expression of the α1β2γ2 combination of subunits in HEK 293 cells produces 6-fold greater current than similar subunits compositions containing mutant α1 subunits. The mutation also results in greatly decreased sensitivity in the receptor for activation by GABA.[2] This combination of mutant containing receptors also activates far more slowly than wild-type containing receptors. Although originally not reported to result in altered protein trafficking, more recent study has indicated that the A322D mutation reduced α1 subunit trafficking to the membrane by >90%. Heterozygous expression of wild-type and mutant subunits produces current approximately 50% the size of wild-type due to this altered trafficking.[3][4] The GABAA receptor is one of the three ligand-gated ion channels responsible for mediating the effects of Gamma-AminoButyric Acid (GABA), the major inhibitory neurotransmitter in the brain. ...
Human Embryonic Kidney cells, also known as HEK cells, HEK 293 or just 293 cells, are an epithelial cell line originally derived, as their name indicates, from embryonic human kidney. ...
Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model...
CLCN2 The CLCN2 gene encodes a chloride channel that is heavily expressed in brain regions inhibited by GABA. It is believed to be important in maintaining a proper chloride reversal potential needed in inhibitory neurotransmission by GABA. There are three known mutations in CLCN2 associated with JME, M200fsX231, 74_117del, and G715E. Neither the M200fsX231 nor the 74_117del mutation yield current when expressed in cells. Since these channels are responsible for the removal of intracellular chloride, these mutations are expected to lead to increased chloride concentrations and, thus, altered chloride reversal potential (ECl). As chloride is conducted through the normally inhibitory GABA receptors, this alteration in ECl may lead to either decreased GABAergic currents or GABAergic currents that are actually excitatory. The G715E mutation, on the other hand, produces normal sized currents but has altered voltage dependent activation. For this mutant, activation occurs at more positive potentials compared to wild-type channels. This may cause increased neuronal excitability.[5] Ion channels are present in the membranes that surround all biological cells. ...
Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model...
The chloride ion is formed when the element chlorine picks up one electron to form an anion (negatively-charged ion) Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. ...
This article discusses the term in the context of biological membranes. ...
GABRD GABRD encodes the δ subunit of the GABA receptor, which is a subunit yielding receptors which do not desensitize and are localized outside of the synapse. There are three mutations in this gene associated with JME, E177A, R220C, and R220H, all located in the N-terminus of the protein. The last of these mutations is also present in normal controls. Receptors containing the E177A mutation have greatly decreased current compared to wild-type. This is not the case for the R220C mutation but is similar to the R220H mutation, though to a lesser extent than the E177A mutation.[6] More recent study has found that the E177A mutant also has greatly decreased desensitization compared to wild-type receptors. Receptors containing only E177A or R220H mutants, versus heterozygotes, had significantly decreased surface expression compared to wild-type or heterozygotic receptors. These mutants also have decreased single-channel open times compared to wild-type.[7] It should be noted, however, that these mutations are very rare as causes of JME.[8] The GABA receptors are a group of receptors with γ-aminobutyric acid (GABA) as their endogenous ligand. ...
Desensitization is a method to reduce or eliminate an organisms negative reaction to a substance or stimulus. ...
Illustration of the major elements in a prototypical synapse. ...
Desensitization is a method to reduce or eliminate an organisms negative reaction to a substance or stimulus. ...
EFHC1 The final known associated gene is EFHC1, which is poorly understood. EFHC1 has three DM10 domains (themselves of unknown function) and an EF hand motif, which is known to bind intracellular calcium. EFHC1 is expressed in many tissues, including the brain, where it is localized to the soma and dendrites of neurons, particularly the hippocampal CA1 region, pyramidal neurons in the cerebral cortex, and Purkinje cells in the cerebellum. There are 5 mutations in EFHC1 associated with JME; D210N, F229L, D253Y, P77T and R221H. The last two mutations were originally detected as a pair in the same individual. EFHC1 seems to be involved in programmed cell death as EFHC1 transfected cells have a higher rate of apoptosis. This rate is decreased by the double mutations P77T + R221H. Interestingly, wild-type EFHC1 increased the R-type calcium channel currents in transfected cells. This stimulation is decreased by JME associated mutations. Because of this, programmed cell death is decreased and the pruning of unwanted neurons may be hampered.[9][10] As with some other loci, mutations in EFHC1 is not a common loci for JME. More recently, R221H has been found without P77T in one JME kindred.[11] For other uses, see Calcium (disambiguation). ...
This article is about the Vedic plant and ritual. ...
Dendrites (from Greek dendron, “treeâ€) are the branched projections of a neuron that act to conduct the electrical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. ...
For other uses, see Hippocampus (disambiguation). ...
For other uses, see Cortex. ...
Drawing of pigeon Purkinje cells (A) by Santiago Ramon y Cajal Purkinje cells are a class of GABAergic neuron located in the cerebellar cortex. ...
The cerebellum (Latin: little brain) is a region of the brain that plays an important role in the integration of sensory perception and motor control. ...
Programmed cell death (PCD) is the deliberate suicide of an unwanted cell in a multicellular organism. ...
A section of mouse liver showing an apoptotic cell indicated by an arrow Apoptosis (pronounced apo tÅ sis) is a process of suicide by a cell in a multicellular organism. ...
Ion channels are present in the membranes that surround all biological cells. ...
Other loci There is also evidence linking a gene or genes on chromosome 15 (15q14) and chromosome 6 (6p21) to JME. Causative genes in this region, however, have not been shown.
Diagnosis Diagnosis is typically made based on patient history. EEG recordings are also sometimes used as confirmation. EEG can mean: Electroencephalography - the method and science of recording and interpreting traces of brain electrical activity as recorded from the skull surface or the device used to record such traces Emperor Entertainment Group - A Hong Kong entertainment company. ...
Treatment/Management See the equivalent section in the main epilepsy article. Before giving Carbamazepine do ask for history of early morning fits especially in a young person. Carbamazepine aggravates these. This article is about the neurological disorder as it affects humans. ...
References - ^ Escayg A, De Waard M, Lee D, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler M (2000). "Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.". Am J Hum Genet 66 (5): 1531-9. PMID 10762541.
- ^ Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire J, Carmant L, Verner A, Lu W, Wang Y, Rouleau G (2002). "Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.". Nat Genet 31 (2): 184-9. PMID 11992121.
- ^ Gallagher M, Song L, Arain F, Macdonald R (2004). "The juvenile myoclonic epilepsy GABA(A) receptor alpha1 subunit mutation A322D produces asymmetrical, subunit position-dependent reduction of heterozygous receptor currents and alpha1 subunit protein expression.". J Neurosci 24 (24): 5570-8. PMID 15201329.
- ^ Krampfl K, Maljevic S, Cossette P, Ziegler E, Rouleau G, Lerche H, Bufler J (2005). "Molecular analysis of the A322D mutation in the GABA receptor alpha-subunit causing juvenile myoclonic epilepsy.". Eur J Neurosci 22 (1): 10-20. PMID 16029191.
- ^ Haug K, Warnstedt M, Alekov A, Sander T, Ramírez A, Poser B, Maljevic S, Hebeisen S, Kubisch C, Rebstock J, Horvath S, Hallmann K, Dullinger J, Rau B, Haverkamp F, Beyenburg S, Schulz H, Janz D, Giese B, Müller-Newen G, Propping P, Elger C, Fahlke C, Lerche H, Heils A (2003). "Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.". Nat Genet 33 (4): 527-32. PMID 12612585.
- ^ Dibbens L, Feng H, Richards M, Harkin L, Hodgson B, Scott D, Jenkins M, Petrou S, Sutherland G, Scheffer I, Berkovic S, Macdonald R, Mulley J (2004). "GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies.". Hum Mol Genet 13 (13): 1315-9. PMID 15115768.
- ^ Feng H, Kang J, Song L, Dibbens L, Mulley J, Macdonald R (2006). "Delta subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of alpha4beta2delta GABAA receptors.". J Neurosci 26 (5): 1499-506. PMID 16452673.
- ^ Lenzen K, Heils A, Lorenz S, Hempelmann A, Sander T (2005). "Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy.". Epilepsy Res 65 (1-2): 53-7. PMID 16023832.
- ^ Suzuki T, Delgado-Escueta A, Aguan K, Alonso M, Shi J, Hara Y, Nishida M, Numata T, Medina M, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey J, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K (2004). "Mutations in EFHC1 cause juvenile myoclonic epilepsy.". Nat Genet 36 (8): 842-9. PMID 15258581.
- ^ Suzuki T, Delgado-Escueta A, Alonso M, Morita R, Okamura N, Sugimoto Y, Bai D, Medina M, Bailey J, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Ochoa A, Jara-Prado A, Inazawa J, Yamakawa K (2006). "Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.". Neurosci Lett 405 (1-2): 126-31. PMID 16876319.
- ^ "Mutations in the GABRA1 and EFHC1 genes are rare in familial juvenile myoclonic epilepsy.". Epilepsy Res. PMID 16839746.
|
Feeds |
Contact