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Hans H Jung - One of the best experts on this subject based on the ideXlab platform.
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life expectancy and mortality in chorea acanthocytosis and McLeod Syndrome
2019Co-Authors: Ruth H. Walker, Hans H Jung, Marcelo Miranda, Adrian DanekAbstract:Abstract Objective To document life expectancy and causes of death in chorea-acanthocytosis (ChAc) and McLeod Syndrome (MLS). Methods We reviewed our personal databases and the published literature to identify cases of ChAc and MLS for whom adequate information was available regarding ages of disease onset and death, cause of death, and other clinical information. Results Adequate information was obtained on 52 patients with ChAc and 34 with MLS. Causes of death included pneumonia, cardiac disease, seizure, suicide, and sepsis. Mean disease duration from diagnosis was 11 years for ChAc, while for MLS it was 21 years. Conclusions Given the current data, causes of death in ChAc and MLS are similar to those for the phenotypically similar Huntington's disease, with additional risks due to the presence of seizures and cardiac disease. Suicidality was seen in 10% of patients with ChAc. Identifying causes of mortality is valuable for disease management and ultimately for clinical trials. In the absence of disease-modifying agents, disease management should focus upon treating symptoms which may contribute to morbidity.
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molecular basis and clinical overview of McLeod Syndrome compared with other neuroacanthocytosis Syndromes a review
2018Co-Authors: Eileen Roulis, Hans H Jung, Catherine A Hyland, Robert L Flower, Christoph Gassner, Beat M FreyAbstract:Importance McLeod Syndrome, encoded by the geneXK, is a rare and progressive disease that shares important similarities with Huntington disease but has widely varied neurologic, neuromuscular, and cardiologic manifestations. Patients with McLeod Syndrome have a distinct hematologic presentation with specific transfusion requirements. Because of its X-linked location, loss of theXKgene or pathogenic variants in this gene are principally associated with the McLeod blood group phenotype in male patients. The clinical manifestation of McLeod Syndrome results from allelic variants of theXKgene or as part of a contiguous gene deletion Syndrome involvingXKand adjacent genes, including those for chronic granulomatous disease, Duchenne muscular dystrophy, and retinitis pigmentosa. McLeod Syndrome typically manifests as neurologic and cardiologic symptoms that evolve in individuals beginning at approximately 40 years of age. Observations Diagnosis of McLeod Syndrome encompasses a number of specialties, including neurology and transfusion medicine. However, information regarding the molecular basis of the Syndrome is incomplete, and clinical information is difficult to find. The International Society of Blood Transfusion has recently compiled and curated a listing ofXKalleles associated with the McLeod phenotype. Of note, McLeod Syndrome caused by structural variants as well as those cases diagnosed as part of a contiguous gene deletion Syndrome were previously classified under a singular allele designation. Conclusions and Relevance This review discusses the clinical manifestations and molecular basis of McLeod Syndrome and provides a comprehensive listing of alleles with involvement in the Syndrome published to date. This review highlights the clinical diversity of McLeod Syndrome and discusses the development of molecular tools to elucidate genetic causes of disease. A more precise and systematic genetic classification is the first step toward correlating and understanding the diverse phenotypic manifestations of McLeod Syndrome and may guide clinical treatment of patients and support for affected and carrier family members. This review provides a knowledge base for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.
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withdrawn novel xp21 1 deletion associated with unusual features in a large McLeod Syndrome kindred
2018Co-Authors: Olafur Sveinsson, Christoph Gassner, Bjarne Udd, Per Svenningsson, Charlotte Engstrom, Jose Miguel Laffitamesa, Goran Solders, Stellan Hertegard, Irina Savitcheva, Hans H JungAbstract:McLeod Syndrome (MLS) is a rare adult-onset, progressive and incurable X-linked multisystemic disorder characterized by chorea, cognitive decline, seizures, polyneuropathy, myopathy and dilated cardiomyopathy with subsequent heart failure and increased risk for arrhythmia [1]. Variable psychiatric symptoms are common; the presence of acanthocytes on blood smears, elevated CK levels and striatal atrophy are other features. MLS is caused by mutation in the XK gene which encodes a membrane transport protein containing the Kx erythrocyte antigen [1]. So far, less than 200 MLS cases have been reported. In general, women harboring XK mutations rarely manifest symptoms. In addition, myoclonus has not been described in association with MLS and functional imaging studies are scarce.
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identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis. PLoS One 2012
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
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Computational Identification of Phospho-Tyrosine Sub- Networks Related to Acanthocyte Generation in
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
Adrian Danek - One of the best experts on this subject based on the ideXlab platform.
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Neurofilament light chain in serum is significantly increased in chorea-acanthocytosis.
2020Co-Authors: Kevin Peikert, Adrian Danek, Katja Akgün, Christian Beste, Tjalf Ziemssen, Carsten Buhmann, Andreas HermannAbstract:Abstract Introduction Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease, characterized by hyper- and hypokinetic movement disorders, peripheral neuropathy and acanthocytosis. Biomarkers are not established; possible candidates include neurofilament reflecting neuroaxonal damage. Methods We studied serum neurofilament light chain (sNfL) of six ChAc patients compared to two healthy control cohorts (A, six age/sex matched and B, historical cohort of 59 healthy adult subjects) and in two patients with the very similar condition of McLeod Syndrome (MLS), the second core Syndrome of neuroacanthocytosis. sNfL was quantified using single-molecule array analysis. Results sNfL concentration was significantly higher in the ChAc cohort (18.73 pg/ml; IQR 15.65–27.70) compared to both healthy control cohorts (A, 7.37 pg/ml; IQR 5.60–9.05; B, 3.10 pg/ml; IQR 2.43–3.98). In MLS patients, a similar sNfL increase was observed. Conclusions sNfL is significantly increased in ChAc and MLS and seems to reflect neuroaxonal damage in the peripheral as well as the central nervous system.
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life expectancy and mortality in chorea acanthocytosis and McLeod Syndrome
2019Co-Authors: Ruth H. Walker, Hans H Jung, Marcelo Miranda, Adrian DanekAbstract:Abstract Objective To document life expectancy and causes of death in chorea-acanthocytosis (ChAc) and McLeod Syndrome (MLS). Methods We reviewed our personal databases and the published literature to identify cases of ChAc and MLS for whom adequate information was available regarding ages of disease onset and death, cause of death, and other clinical information. Results Adequate information was obtained on 52 patients with ChAc and 34 with MLS. Causes of death included pneumonia, cardiac disease, seizure, suicide, and sepsis. Mean disease duration from diagnosis was 11 years for ChAc, while for MLS it was 21 years. Conclusions Given the current data, causes of death in ChAc and MLS are similar to those for the phenotypically similar Huntington's disease, with additional risks due to the presence of seizures and cardiac disease. Suicidality was seen in 10% of patients with ChAc. Identifying causes of mortality is valuable for disease management and ultimately for clinical trials. In the absence of disease-modifying agents, disease management should focus upon treating symptoms which may contribute to morbidity.
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current state of knowledge in chorea acanthocytosis as core neuroacanthocytosis Syndrome
2017Co-Authors: Kevin Peikert, Adrian Danek, Andreas HermannAbstract:Abstract Neuroacanthocytosis (NA) Syndromes are a group of rare diseases characterized by neurological disorders and misshaped spiky red blood cells (acanthocytes) including Chorea-Acanthocytosis (ChAc), McLeod Syndrome (MLS), Huntington disease-like 2 (HDL 2), pantothenate kinase-associated neurodegeneration (PKAN), abeta- and hypobetalipoproteinemia and aceruloplasminemia. This clinically and genetically heterogeneous group of diseases shares main clinical features presenting most often as a hyperkinetic movement disorder. Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms. The current review focuses upon ChAc as the core entity of NA Syndromes caused by mutations in the VPS13A gene. The support of patient organizations and the ERA-NET initiative yielded to different multidisciplinary efforts with significant progress on our understanding of ChAc. Disturbances in two pathways are currently considered to be significantly involved in the pathophysiology of ChAc, namely elevated Lyn kinase phosphorylation and decreased signaling via Phosphoinositide 3-kinase (PI3K). These recent developments may reveal potential drugable targets for causative therapies of ChAc.
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identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis. PLoS One 2012
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
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Alterations of Red Cell Membrane Properties in
2016Co-Authors: Claudia Siegl, Benedikt Bader, Adrian Danek, Patricia Hamminger, Herbert Jank, Uwe Ahting, Allison Gregory, Monika Hartig, Susan Hayflick, Andreas HermannAbstract:Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea acanthocytosis (ChAc), McLeod Syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasm
Ruth H. Walker - One of the best experts on this subject based on the ideXlab platform.
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life expectancy and mortality in chorea acanthocytosis and McLeod Syndrome
2019Co-Authors: Ruth H. Walker, Hans H Jung, Marcelo Miranda, Adrian DanekAbstract:Abstract Objective To document life expectancy and causes of death in chorea-acanthocytosis (ChAc) and McLeod Syndrome (MLS). Methods We reviewed our personal databases and the published literature to identify cases of ChAc and MLS for whom adequate information was available regarding ages of disease onset and death, cause of death, and other clinical information. Results Adequate information was obtained on 52 patients with ChAc and 34 with MLS. Causes of death included pneumonia, cardiac disease, seizure, suicide, and sepsis. Mean disease duration from diagnosis was 11 years for ChAc, while for MLS it was 21 years. Conclusions Given the current data, causes of death in ChAc and MLS are similar to those for the phenotypically similar Huntington's disease, with additional risks due to the presence of seizures and cardiac disease. Suicidality was seen in 10% of patients with ChAc. Identifying causes of mortality is valuable for disease management and ultimately for clinical trials. In the absence of disease-modifying agents, disease management should focus upon treating symptoms which may contribute to morbidity.
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identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis. PLoS One 2012
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
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Untangling the Thorns: Advances in the Neuroacantho- cytosis Syndromes
2016Co-Authors: Ruth H. WalkerAbstract:There have been significant advances in neuroac-anthocytosis (NA) Syndromes in the past 20 years, however, confusion still exists regarding the pre-cise nature of these disorders and the correct no-menclature. This article seeks to clarify these is-sues and to summarise the recent literature in the field. The four key NA Syndromes are described here–chorea-acanthocytosis, McLeod Syndrome, Huntington’s disease-like 2, and pantothenate ki-nase-associated neurodegeneration. In the first two, acanthocytosis is a frequent, although not in-variable, finding; in the second two, it occurs in ap-proximately 10 % of patients. Degeneration affect-ing the basal ganglia is the key neuropathologi
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Reviews Management of Neuroacanthocytosis Syndromes
2016Co-Authors: Ruth H. WalkerAbstract:Background: The two core neuroacanthocytosis (NA) Syndromes, chorea-acanthocytosis (ChAc) and McLeod Syndrome, are progressive neurodegenerative disorders that primarily affect the basal ganglia. The characteristic phenotype comprises a variety of movement disorders including chorea, dystonia, and parkinsonism, as well as psychiatric and cognitive symptoms attributable to basal ganglia dysfunction. These disorders are symptomatically managed on a case-by-case basis, with very few practitioners seeing more than a single case in their careers. Methods: A literature search was performed on PubMed utilizing the terms neuroacanthocytosis, chorea-acanthocytosis, and McLeod Syndrome, and articles were reviewed for mentions of therapies, successful or otherwise. Results: There have been no blinded, controlled trials and only one retrospective case series describing ChAc. The various therapies that have been used in patients with NA Syndromes are summarized. Discussion: Management remains at present purely symptomatic, which is similar in principle to other more common basal ganglia neurodegenerative disorders such as Huntington’s disease (HD) and Parkinson’s disease (PD). However, there are some specific issues particular to NA Syndromes that merit attention. A
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Computational Identification of Phospho-Tyrosine Sub- Networks Related to Acanthocyte Generation in
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
Lucia De Franceschi - One of the best experts on this subject based on the ideXlab platform.
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identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis. PLoS One 2012
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
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Computational Identification of Phospho-Tyrosine Sub- Networks Related to Acanthocyte Generation in
2016Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis Syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod Syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b
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Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis Syndromes.
2014Co-Authors: Lucia De Franceschi, Giel J. C. G. M. Bosman, Narla MohandasAbstract:PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod Syndrome (MLS). RECENT FINDINGS: Although molecular defects associated with neuroacanthocytosis have been identified recently, their pathophysiology and the related RBC abnormalities are largely unknown. Studies in ChAc RBCs have shown an altered association between the cytoskeleton and the integral membrane protein compartment in the absence of major changes in RBC membrane composition. In ChAc RBCs, abnormal Lyn kinase activation in a Syk-independent fashion has been reported recently, resulting in increased band 3 tyrosine phosphorylation and perturbation of the stability of the multiprotein band 3-based complexes bridging the membrane to the spectrin-based membrane skeleton. Similarly, in MLS, the absence of XK-protein, which is associated with the spectrin-actin-4.1 junctional complex, is associated with an abnormal membrane protein phosphorylation state, with destabilization of the membrane skeletal network resulting in generation of acanthocytes. SUMMARY: A novel mechanism in generation of acanthocytes involving abnormal Lyn activation, identified in ChAc, expands the acanthocytosis phenomenon toward protein-protein interactions, controlled by phosphorylation-related abnormal signaling.
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Demographic and molecular data of control subjects and McLeod Syndrome and chorea-acanthocytosis patients.
2012Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:M; male; F: female; yrs: years; ChAc: chorea-acanthocytosis; MLS: McLeod Syndrome; Control age is presented as means ± SD. Molecular defect” refers to the VPS13A and XK gene, respectively, that are responsible for ChAc and MLS.
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DUSP13 shortest paths to dephosphorylated proteins in Xk_to_P-tyr-network.
2012Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela SicilianoAbstract:Graph of all shortest paths linking DUSP13 to INMT, PRPH, PRDX6 and ANXA4. A distance of 3 (ANXA4) or 4 (INMT, PRPH, PRDX6) degree separates DUSP13 from the proteins found dephosphorylated in red cell from patients with McLeod Syndrome (MLS).
Marion E. Reid - One of the best experts on this subject based on the ideXlab platform.
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McLeod phenotype without the McLeod Syndrome
2007Co-Authors: Ruth H. Walker, Adrian Danek, Marion E. Reid, I Uttner, Robert Offner, Soohee LeeAbstract:BACKGROUND: McLeod neuroacanthocytosis Syndrome is a late-onset X-linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype-genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. STUDY DESIGN AND METHODS: Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod Syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. RESULTS: Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. CONCLUSIONS: The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.
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a case of McLeod Syndrome with unusually severe myopathy
1999Co-Authors: Tadataka Kawakami, Marion E. Reid, Yoshihisa Takiyama, Kumi Sakoe, T Ogawa, Toru Yoshioka, Masatoyo Nishizawa, Osamu Kobayashi, Ikuya Nonaka, Imaharu NakanoAbstract:A 51-year-old man developed weakness and muscle atrophy in the legs at the age of 41, later followed by choreiform involuntary movements. Neurological and laboratory examinations revealed severe muscle weakness and atrophy, and areflexia in all the extremities, acanthocytosis and an elevated serum creatine kinase level. Together with these findings, the weak expression of Kell blood group antigens and the absence of the Kx antigen led to a definite diagnosis of McLeod Syndrome for his condition. Brain magnetic resonance imaging revealed marked atrophy of the head of the caudate nuclei. Although immunocytochemical analysis of dystrophin in muscle specimens from our patient revealed normal staining, we found prominent fiber size variability, central nuclei, and connective tissue proliferation as well as necrotic and regenerating fibers, which are as a whole compatible with the myopathology of muscular dystrophy. Moreover, muscle computerized tomography of the lower extremities revealed the 'selectivity pattern' characteristically reported in muscular dystrophies including Duchenne type muscular dystrophy. The muscular symptoms and pathology in McLeod Syndrome have been reported to be mild, but the present case clearly shows that the muscular features in this condition may be much more severe than previously thought.
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A family of McLeod Syndrome, masquerading as chorea-acanthocytosis
1994Co-Authors: Hiroshi Takashima, Tetsuo Sakai, Hiroshi Iwashita, Yuki Matsuda, Kaoru Tanaka, Kenichiro Oda, Yasuto Okubo, Marion E. ReidAbstract:Abstract A man, aged 52, is reported to show (1) adult onset, (2) progressive orofacial dyskinesia and choreic movements of the extremities, (3) tongue biting, (4) denervation of the peripheral nerves, (5) acanthocytosis, and (6) increased serum creatine kinase, which are characteristic of chorea-acanthocytosis. The Kell blood group examination on erythrocytes disclosed that the propositus had McLeod phenotype, and his mother and one of his sisters werecarriers of the McLeod phenotype. Thus, he was diagnosed as having McLeod Syndrome. A criterion of exclusion of McLeod phenotype on erythrocytes should be added to the diagnostic criteria of chorea-acanthocytosis. Moreover, chronic neurogenic changes instead of myogenic changes were electromyographically and histopathologically verified in the muscle.