The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform

Ruey-meei Wu - One of the best experts on this subject based on the ideXlab platform.

  • A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome
    Journal of Human Genetics, 2010
    Co-Authors: Hoi-fong Chan, Meng-ling Chen, Jen-jen Su, Li-chin Ko, Ruey-meei Wu
    Abstract:

    Andersen–Tawil syndrome (ATS) is a rare familial Potassium Channelopathy characterized by the clinical triad of periodic paralysis, cardiac arrhythmia and dysmorphic facial/skeletal features. The majority of ATS patients are caused by mutations of the KCNJ2 gene, which encodes the inward-rectifying Potassium channel protein Kir2.1. However, the effects of the KCNJ2 mutation on the central nervous system are rarely studied. In this report, we describe a heterozygous missense mutation (p.Thr192Ile) in the KCNJ2 gene, which segregates with the disease phenotype in an ATS family. It is noted that in addition to the classical clinical phenotypes of ATS, the index patient exhibited major depression and pyramidal tract signs with diffuse periventricular white matter lesions without contrast enhancement. This mutation and the unusual clinical manifestations observed underscore the phenotypic complexity underlying ATS. Our observations expand the current knowledge of the phenotypic variability of ATS caused by the KCNJ2 mutation. Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement.

  • A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen-Tawil syndrome.
    Journal of Human Genetics, 2010
    Co-Authors: Hoi-fong Chan, Meng-ling Chen, Jen-jen Su, Li-chin Ko, Ruey-meei Wu
    Abstract:

    Andersen–Tawil syndrome (ATS) is a rare familial Potassium Channelopathy characterized by the clinical triad of periodic paralysis, cardiac arrhythmia and dysmorphic facial/skeletal features. The majority of ATS patients are caused by mutations of the KCNJ2 gene, which encodes the inward-rectifying Potassium channel protein Kir2.1. However, the effects of the KCNJ2 mutation on the central nervous system are rarely studied. In this report, we describe a heterozygous missense mutation (p.Thr192Ile) in the KCNJ2 gene, which segregates with the disease phenotype in an ATS family. It is noted that in addition to the classical clinical phenotypes of ATS, the index patient exhibited major depression and pyramidal tract signs with diffuse periventricular white matter lesions without contrast enhancement. This mutation and the unusual clinical manifestations observed underscore the phenotypic complexity underlying ATS. Our observations expand the current knowledge of the phenotypic variability of ATS caused by the KCNJ2 mutation. Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement.

Wei Du - One of the best experts on this subject based on the ideXlab platform.

  • calcium sensitive Potassium Channelopathy in human epilepsy and paroxysmal movement disorder
    Nature Genetics, 2005
    Co-Authors: Wei Du, Jocelyn F Bautista, Huanghe Yang, Ana Diezsampedro, Lejin Wang, Prakash Kotagal
    Abstract:

    The large conductance calcium-sensitive Potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the a subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in openchannel probability due to a three- to fivefold increase in Ca 2+ sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease. Epilepsy is one of the most common and debilitating neurological disorders, affecting more than 40 million people worldwide 1 .P aroxysmal dyskinesias are another heterogeneous group of neurological disorders characterized by sudden, unpredictable, disabling attacks of involuntary movement often requiring life-long treatment. The coexistence of epilepsy and paroxysmal dyskinesia in the same individual or family is an increasingly recognized phenomenon 2,3 . The basic pathophysiology underlying the coexistence of epilepsy and paroxysmal dyskinesia is unknown, and no specific gene has been associated with it. We studied a large family with coexistent generalized epilepsy and

Michael G. Hanna - One of the best experts on this subject based on the ideXlab platform.

  • Episodic ataxia type 1: A neuronal Potassium Channelopathy
    Neurotherapeutics, 2007
    Co-Authors: Sanjeev Rajakulendran, Stephanie Schorge, Dimitri M. Kullmann, Michael G. Hanna
    Abstract:

    Episodic ataxia type 1 is a paroxysmal neurological disorder characterized by short-lived attacks of recurrent midline cerebellar dysfunction and continuous motor activity. Mutations in KCN1A , the gene encoding Kv1.1, a voltage-gated neuronal Potassium channel, are associated with the disorder. Although rare, the syndrome highlights the fundamental features of genetic ion-channel diseases and serves as a useful model for understanding more common paroxysmal disorders, such as epilepsy and migraine. This review examines our current understanding of episodic ataxia type 1, focusing on its clinical and genetic features, pathophysiology, and treatment.

  • Clinical, genetic, and expression studies of mutations in the Potassium channel gene KCNA1 reveal new phenotypic variability
    Annals of Neurology, 2000
    Co-Authors: L H Eunson, Sameer M. Zuberi, S. Youroukos, C. P. Panayiotopoulos, Rocco Liguori, Patrizia Avoni, Robert Mcwilliam, John Stephenson, Michael G. Hanna
    Abstract:

    Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system Potassium Channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage-gated Potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug-resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed-rectifier type Potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the Potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study.

Kimiyoshi Arimura - One of the best experts on this subject based on the ideXlab platform.

  • Isaacs' syndrome as a Potassium Channelopathy of the nerve.
    Muscle & nerve. Supplement, 2020
    Co-Authors: Kimiyoshi Arimura, Yoshito Sonoda, Osamu Watanabe, Tatsui Nagado, Asutsugu Kurono, Hisanori Tomimitsu, Reika Otsuka, Masaki Kameyama, Mitsuhiro Osame
    Abstract:

    Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated Potassium channel disorder (Channelopathy). The target channel proteins of the antigens are voltage-gated Potassium channels (VGKCs), especially dendrotoxin-sensitive fast Potassium channels. The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of Potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology.

  • Isaacs' syndrome, stiff person syndrome and Satoyoshi disease: pathomechanisms and treatment
    Rinshō shinkeigaku Clinical neurology, 2004
    Co-Authors: Kimiyoshi Arimura
    Abstract:

    : Neurological disorders with characteristic clinical manifestations of painful muscle cramp and stiffness are not infrequent. The immune-mediated mechanism with specific antibodies among these diseases is particularly important for treatment. Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated Potassium Channelopathy. The suppression of voltage-gated Potassium channel (VGKC) by antibodies induces peripheral nerve hyperexcitability. Antibodies may decrease VGKC density by cross-linking F (ab)2 fractions and increasing the degradation rate of VGKCs. Stiff person syndrome (SPS) and its variants show characteristic symptoms and signs of central nervous system hyperexcitability due to antibodies to the GABA-ergic system such as glutamic acid decarboxylase (GAD), amphiphysin 1 and gephyrin. The role of GAD is the subject of debate, however, recent studies reveal the intrathecal synthesis of GAD which is specific for SPS and appears to impair GABA synthesis. Satoyoshi disease is characterized by painful muscle cramp, baldness, intractable diarrhea, bone and joint deformity, and endocrine disturbances. Muscle cramp may be due to inhibition of the spinal interneuron and hyperexciatability of the anterior horn cell. In patients with Satoyoshi disease, sera reacted with an 85 kDa protein of human brain lysate. In all these disorders, suppression or removal of specific antibodies is critical, however, the effects are short-lived, and supplemental treatment to reduce the hyperexcitability of the peripheral or central nervous system will be needed.

  • isaacs syndrome as a Potassium Channelopathy of the nerve
    Muscle & Nerve, 2002
    Co-Authors: Kimiyoshi Arimura, Yoshito Sonoda, Osamu Watanabe, Tatsui Nagado, Asutsugu Kurono, Hisanori Tomimitsu, Reika Otsuka, Masaki Kameyama, Mitsuhiro Osame
    Abstract:

    Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated Potassium channel disorder (Channelopathy). The target channel proteins of the antigens are voltage-gated Potassium channels (VGKCs), especially dendrotoxin-sensitive fast Potassium channels. The suppression of voltage-gated outward K+ current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of Potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S55–S58, 2002

  • Antibodies directed to voltage-gated Potassium channels in sera from acquired neuromyotonia and related disorders
    Rinshō shinkeigaku Clinical neurology, 1999
    Co-Authors: Kimiyoshi Arimura
    Abstract:

    : Anti-voltage-gated Potassium channel (VGKC) antibodies were measured in sera from 21 patients with acquired neuromyotonia (Isaacs syndrome) and related disorders. Seventeen of 21 sera suppressed Potassium currents of neuroblastoma cell line (NB-1) using the patch clamp method, and the finding is mostly correlated with myokymic discharge in electromyography. Regarding the pathophysiology of suppression of VGKC, we investigated the effects of sera from 2 ANM patients on channel kinetics using the patch clamp method. The activation and inactivation kinetics of the Potassium current were not altered by patients' immunoglobulins. We also investigated the effect of patients' sera on different VGKC subtypes using hKv1.1 and 1.6 transfected CHO cells. The same patients' sera suppressed the expressed VGKCs. Our results suggest that anti-VGKC antibodies may be positive not only in patients with classical ANM (Isaacs syndrome) but also in patients with related disorders who did not fulfill the characteristic symptoms. These disorders may be categorized as Potassium Channelopathy of the peripheral nervous system. The pathophysiology of the suppression of VGKC by antibodies is not the direct effect on channel kinetic but due to increased degradation or reduced production of VGKC. Epitopes of Anti-VGKC antibodies are still unclear.

Mitsuhiro Osame - One of the best experts on this subject based on the ideXlab platform.

  • Isaacs' syndrome as a Potassium Channelopathy of the nerve.
    Muscle & nerve. Supplement, 2020
    Co-Authors: Kimiyoshi Arimura, Yoshito Sonoda, Osamu Watanabe, Tatsui Nagado, Asutsugu Kurono, Hisanori Tomimitsu, Reika Otsuka, Masaki Kameyama, Mitsuhiro Osame
    Abstract:

    Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated Potassium channel disorder (Channelopathy). The target channel proteins of the antigens are voltage-gated Potassium channels (VGKCs), especially dendrotoxin-sensitive fast Potassium channels. The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of Potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology.

  • isaacs syndrome as a Potassium Channelopathy of the nerve
    Muscle & Nerve, 2002
    Co-Authors: Kimiyoshi Arimura, Yoshito Sonoda, Osamu Watanabe, Tatsui Nagado, Asutsugu Kurono, Hisanori Tomimitsu, Reika Otsuka, Masaki Kameyama, Mitsuhiro Osame
    Abstract:

    Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated Potassium channel disorder (Channelopathy). The target channel proteins of the antigens are voltage-gated Potassium channels (VGKCs), especially dendrotoxin-sensitive fast Potassium channels. The suppression of voltage-gated outward K+ current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of Potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S55–S58, 2002