The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis

Department of Neuropsychiatry, Hirosaki University, Khirosaki, Aomori, Japan
Nature Genetics (Impact Factor: 29.35). 07/2001; 28(2):121-2. DOI: 10.1038/88825
Source: PubMed


Chorea-acanthocytosis is a neurodegenerative disorder with peripheral red cell acanthocytosis. Linkage of chorea-acanthocytosis to chromosome 9q21 has been found. We refined the locus region and identified a previously unknown, full-length cDNA encoding a presumably structural protein, which we called chorein. We found a deletion in the coding region of the cDNA leading to a frame shift resulting in the production of a truncated protein in both alleles of patients and in single alleles of obligate carriers.

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    • "In particular, VPS13A expression could be detected in those tissues that are related to the clinical condition of ChAc, namely erythroid precursors, skeletal muscle and brain, where equal levels of transcript were found in several areas (including frontal lobe and putamen). At present, 71 VPS13A mutations have been reported [11] [12] [37]. They seem to be evenly distributed throughout the gene with no obvious clustering. "

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    • "Prior to the first NA symposium in 2002, fundamental genetic studies had linked MLS to the causative XK gene14 and Levine–Critchley disease, renamed ChAc, to VPS13A. These studies were performed at the Wellcome Trust Centre for Human Genetics, and their findings were soon independently confirmed by researchers at Kagoshima University.15 "
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    ABSTRACT: When people are diagnosed with rare, incurable disorders, they and their families suffer both from the disease itself and from the lack of information and resources available. They become acutely aware that research can only be conducted when it is funded. This article presents our experiences following the diagnosis of our daughter with chorea-acanthocytosis, and describes how we established a not-for-profit organization to fund and facilitate research into this rare disease. Personal relationships with clinicians and scientists, and with friends who were willing to help, have played an essential part in moving the field of neuroacanthocytosis research forward.
    11/2013; 3.
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    • "Neuroacanthocytosis syndromes currently comprise four subtypes caused by mutations in distinct genes. Chorea-acanthocytosis (ChAc) relates to mutations in VPS13A [3,4], McLeod Syndrome (MLS) has mutations in XK [5], Huntington’s Disease-like 2 (HDL2) in JPH3 [6], and panthotenate kinase-associated neurodegeneration (PKAN) in PANK2 [7]. PKAN is also categorized among the Neurodegeneration with Brain Iron Accumulation (NBIA) syndromes characterized by iron deposition in the basal ganglia typically detected by brain MRI. "
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    ABSTRACT: 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 plasma membrane, namely drug-induced endocytosis, phosphatidylserine exposure and calcium uptake upon treatment with lysophosphatidic acid. ChAc red cell samples clearly showed a reduced response in drug-induced endovesiculation, lysophosphatidic acid-induced phosphatidylserine exposure, and calcium uptake. Impaired responses were also observed in acanthocyte-positive NBIA (PKAN) red cells but not in patient cells without shape abnormalities. These data suggest an "acanthocytic state" of the red cell where alterations in functional and interdependent membrane properties arise together with an acanthocytic cell shape. Further elucidation of the aberrant molecular mechanisms that cause this acanthocytic state may possibly help to evaluate the pathological pathways leading to neurodegeneration.
    PLoS ONE 10/2013; 8(10):e76715. DOI:10.1371/journal.pone.0076715 · 3.23 Impact Factor
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