Clinical spectrum of Kufor‐Rakeb syndrome in the Chilean kindred with ATP13A2 mutations
Identifieur interne : 000733 ( Main/Corpus ); précédent : 000732; suivant : 000734Clinical spectrum of Kufor‐Rakeb syndrome in the Chilean kindred with ATP13A2 mutations
Auteurs : Maria I. Behrens ; Norbert Brüggemann ; Pedro Chana ; Pablo Venegas ; Marianne K Gi ; Teresa Parrao ; Patricia Orellana ; Cristian Garrido ; Cecilia V. Rojas ; Jan Hauke ; Eric Hahnen ; Rafael González ; Nicolas Seleme ; Ver Nica Fernández ; Alexander Schmidt ; Ferdinand Binkofski ; Detlef Kömpf ; Christian Kubisch ; Johann Hagenah ; Christine Klein ; Alfredo RamirezSource :
- Movement Disorders [ 0885-3185 ] ; 2010-09-15.
English descriptors
Abstract
We report the clinical features of the original Chilean family with Kufor‐Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.
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DOI: 10.1002/mds.22996
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Behrens</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Bruggemann, Norbert" sort="Bruggemann, Norbert" uniqKey="Bruggemann N" first="Norbert" last="Brüggemann">Norbert Brüggemann</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Chana, Pedro" sort="Chana, Pedro" uniqKey="Chana P" first="Pedro" last="Chana">Pedro Chana</name><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Centro de Estudios del Movimiento, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Venegas, Pablo" sort="Venegas, Pablo" uniqKey="Venegas P" first="Pablo" last="Venegas">Pablo Venegas</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="K Gi, Marianne" sort="K Gi, Marianne" uniqKey="K Gi M" first="Marianne" last="K Gi">Marianne K Gi</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Parrao, Teresa" sort="Parrao, Teresa" uniqKey="Parrao T" first="Teresa" last="Parrao">Teresa Parrao</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Orellana, Patricia" sort="Orellana, Patricia" uniqKey="Orellana P" first="Patricia" last="Orellana">Patricia Orellana</name><affiliation><mods:affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Garrido, Cristian" sort="Garrido, Cristian" uniqKey="Garrido C" first="Cristian" last="Garrido">Cristian Garrido</name><affiliation><mods:affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Rojas, Cecilia V" sort="Rojas, Cecilia V" uniqKey="Rojas C" first="Cecilia V." last="Rojas">Cecilia V. 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Behrens</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Bruggemann, Norbert" sort="Bruggemann, Norbert" uniqKey="Bruggemann N" first="Norbert" last="Brüggemann">Norbert Brüggemann</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Chana, Pedro" sort="Chana, Pedro" uniqKey="Chana P" first="Pedro" last="Chana">Pedro Chana</name><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Centro de Estudios del Movimiento, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Venegas, Pablo" sort="Venegas, Pablo" uniqKey="Venegas P" first="Pablo" last="Venegas">Pablo Venegas</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="K Gi, Marianne" sort="K Gi, Marianne" uniqKey="K Gi M" first="Marianne" last="K Gi">Marianne K Gi</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Parrao, Teresa" sort="Parrao, Teresa" uniqKey="Parrao T" first="Teresa" last="Parrao">Teresa Parrao</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation><affiliation><mods:affiliation>Clínica Alemana de Santiago, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Orellana, Patricia" sort="Orellana, Patricia" uniqKey="Orellana P" first="Patricia" last="Orellana">Patricia Orellana</name><affiliation><mods:affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Garrido, Cristian" sort="Garrido, Cristian" uniqKey="Garrido C" first="Cristian" last="Garrido">Cristian Garrido</name><affiliation><mods:affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Rojas, Cecilia V" sort="Rojas, Cecilia V" uniqKey="Rojas C" first="Cecilia V." last="Rojas">Cecilia V. Rojas</name><affiliation><mods:affiliation>Instituto Nutrición y Tecnología Alimentos, Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Hauke, Jan" sort="Hauke, Jan" uniqKey="Hauke J" first="Jan" last="Hauke">Jan Hauke</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hahnen, Eric" sort="Hahnen, Eric" uniqKey="Hahnen E" first="Eric" last="Hahnen">Eric Hahnen</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</mods:affiliation></affiliation></author><author><name sortKey="Gonzalez, Rafael" sort="Gonzalez, Rafael" uniqKey="Gonzalez R" first="Rafael" last="González">Rafael González</name><affiliation><mods:affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Seleme, Nicolas" sort="Seleme, Nicolas" uniqKey="Seleme N" first="Nicolas" last="Seleme">Nicolas Seleme</name><affiliation><mods:affiliation>Departamento de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Fernandez, Ver Nica" sort="Fernandez, Ver Nica" uniqKey="Fernandez V" first="Ver Nica" last="Fernández">Ver Nica Fernández</name><affiliation><mods:affiliation>Departamento de Ciencias Neurológicas Oriente, Servicio Neuro‐Oftalmología, Universidad de Chile, Santiago, Chile</mods:affiliation></affiliation></author><author><name sortKey="Schmidt, Alexander" sort="Schmidt, Alexander" uniqKey="Schmidt A" first="Alexander" last="Schmidt">Alexander Schmidt</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Binkofski, Ferdinand" sort="Binkofski, Ferdinand" uniqKey="Binkofski F" first="Ferdinand" last="Binkofski">Ferdinand Binkofski</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kompf, Detlef" sort="Kompf, Detlef" uniqKey="Kompf D" first="Detlef" last="Kömpf">Detlef Kömpf</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kubisch, Christian" sort="Kubisch, Christian" uniqKey="Kubisch C" first="Christian" last="Kubisch">Christian Kubisch</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hagenah, Johann" sort="Hagenah, Johann" uniqKey="Hagenah J" first="Johann" last="Hagenah">Johann Hagenah</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ramirez, Alfredo" sort="Ramirez, Alfredo" uniqKey="Ramirez A" first="Alfredo" last="Ramirez">Alfredo Ramirez</name><affiliation><mods:affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-09-15">2010-09-15</date><biblScope unit="volume">25</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1929">1929</biblScope><biblScope unit="page" to="1937">1937</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">3750C8F32896C3226E71DA44843798B6E1366124</idno><idno type="DOI">10.1002/mds.22996</idno><idno type="ArticleID">MDS22996</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ATP13A2 mutations</term><term>DNA methylation</term><term>juvenile Parkinsonism</term><term>minimyoclonus</term><term>saccadic pursuit</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We report the clinical features of the original Chilean family with Kufor‐Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Maria I. Behrens MD, PhD</name><affiliations><json:string>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string><json:string>Clínica Alemana de Santiago, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Norbert Brüggemann MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Pedro Chana MD</name><affiliations><json:string>Clínica Alemana de Santiago, Santiago, Chile</json:string><json:string>Centro de Estudios del Movimiento, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Pablo Venegas MD</name><affiliations><json:string>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Marianne Kägi MD</name><affiliations><json:string>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Teresa Parrao BPsych</name><affiliations><json:string>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string><json:string>Clínica Alemana de Santiago, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Patricia Orellana MD</name><affiliations><json:string>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Cristian Garrido MRT</name><affiliations><json:string>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Cecilia V. Rojas PhD</name><affiliations><json:string>Instituto Nutrición y Tecnología Alimentos, Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Jan Hauke MSc</name><affiliations><json:string>Institute of Human Genetics, University of Cologne, Cologne, Germany</json:string></affiliations></json:item><json:item><name>Eric Hahnen PhD</name><affiliations><json:string>Institute of Human Genetics, University of Cologne, Cologne, Germany</json:string></affiliations></json:item><json:item><name>Rafael González SLP</name><affiliations><json:string>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Nicolas Seleme MD</name><affiliations><json:string>Departamento de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Verónica Fernández MD</name><affiliations><json:string>Departamento de Ciencias Neurológicas Oriente, Servicio Neuro‐Oftalmología, Universidad de Chile, Santiago, Chile</json:string></affiliations></json:item><json:item><name>Alexander Schmidt MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Ferdinand Binkofski MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Detlef Kömpf MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Christian Kubisch MD</name><affiliations><json:string>Institute of Human Genetics, University of Cologne, Cologne, Germany</json:string></affiliations></json:item><json:item><name>Johann Hagenah MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Christine Klein MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Alfredo Ramirez MD</name><affiliations><json:string>Department of Neurology, University of Luebeck, Lübeck, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>juvenile Parkinsonism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ATP13A2 mutations</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>minimyoclonus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>saccadic pursuit</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DNA methylation</value></json:item></subject><articleId><json:string>MDS22996</json:string></articleId><language><json:string>eng</json:string></language><abstract>We report the clinical features of the original Chilean family with Kufor‐Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.</abstract><qualityIndicators><score>7.403</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1930</abstractCharCount><pdfWordCount>4403</pdfWordCount><pdfCharCount>31476</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>253</abstractWordCount></qualityIndicators><title>Clinical spectrum of Kufor‐Rakeb syndrome in the Chilean kindred with ATP13A2 mutations</title><genre><json:string>article</json:string></genre><host><volume>25</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>9</total><last>1937</last><first>1929</first></pages><issn><json:string>0885-3185</json:string></issn><issue>12</issue><subject><json:item><value>Research 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Chile</p></note><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><affiliation>Clínica Alemana de Santiago, Santiago, Chile</affiliation></author><author><persName><forename type="first">Norbert</forename><surname>Brüggemann</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Pedro</forename><surname>Chana</surname></persName><roleName type="degree">MD</roleName><affiliation>Clínica Alemana de Santiago, Santiago, Chile</affiliation><affiliation>Centro de Estudios del Movimiento, Santiago, Chile</affiliation></author><author><persName><forename type="first">Pablo</forename><surname>Venegas</surname></persName><roleName type="degree">MD</roleName><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Marianne</forename><surname>Kägi</surname></persName><roleName type="degree">MD</roleName><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Teresa</forename><surname>Parrao</surname></persName><roleName type="degree">BPsych</roleName><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><affiliation>Clínica Alemana de Santiago, Santiago, Chile</affiliation></author><author><persName><forename type="first">Patricia</forename><surname>Orellana</surname></persName><roleName type="degree">MD</roleName><affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Cristian</forename><surname>Garrido</surname></persName><roleName type="degree">MRT</roleName><affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Cecilia V.</forename><surname>Rojas</surname></persName><roleName type="degree">PhD</roleName><affiliation>Instituto Nutrición y Tecnología Alimentos, Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Jan</forename><surname>Hauke</surname></persName><roleName type="degree">MSc</roleName><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation></author><author><persName><forename type="first">Eric</forename><surname>Hahnen</surname></persName><roleName type="degree">PhD</roleName><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation></author><author><persName><forename type="first">Rafael</forename><surname>González</surname></persName><roleName type="degree">SLP</roleName><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Nicolas</forename><surname>Seleme</surname></persName><roleName type="degree">MD</roleName><affiliation>Departamento de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Verónica</forename><surname>Fernández</surname></persName><roleName type="degree">MD</roleName><affiliation>Departamento de Ciencias Neurológicas Oriente, Servicio Neuro‐Oftalmología, Universidad de Chile, Santiago, Chile</affiliation></author><author><persName><forename type="first">Alexander</forename><surname>Schmidt</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Ferdinand</forename><surname>Binkofski</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Detlef</forename><surname>Kömpf</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Christian</forename><surname>Kubisch</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation></author><author><persName><forename type="first">Johann</forename><surname>Hagenah</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Klein</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Alfredo</forename><surname>Ramirez</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. 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KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>juvenile Parkinsonism</term></item><item><term>ATP13A2 mutations</term></item><item><term>minimyoclonus</term></item><item><term>saccadic pursuit</term></item><item><term>DNA methylation</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-11-13">Received</change><change when="2009-12-11">Registration</change><change when="2010-09-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/3750C8F32896C3226E71DA44843798B6E1366124/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. 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xml:id="kwd5">DNA methylation</keyword></keywordGroup><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds22996:MDS_22996_sm_suppvideo"></mediaResource><caption>Supporting Video</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>We report the clinical features of the original Chilean family with Kufor‐Rakeb syndrome (KRS) that led to the discovery of the <i>ATP13A2</i> gene at the PARK9 locus. KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the <i>ATP13A2</i> promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous <i>ATP13A2</i> mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the <i>ATP13A2</i> promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Clinical spectrum of Kufor‐Rakeb syndrome in the Chilean kindred with ATP13A2 mutations</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Kufor‐Rakeb Syndrome in The Chilean Kindred</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Clinical spectrum of Kufor‐Rakeb syndrome in the Chilean kindred with</title></titleInfo><name type="personal"><namePart type="given">Maria I.</namePart><namePart type="family">Behrens</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, 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type="given">Pablo</namePart><namePart type="family">Venegas</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marianne</namePart><namePart type="family">Kägi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Teresa</namePart><namePart type="family">Parrao</namePart><namePart type="termsOfAddress">BPsych</namePart><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><affiliation>Clínica Alemana de Santiago, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patricia</namePart><namePart type="family">Orellana</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cristian</namePart><namePart type="family">Garrido</namePart><namePart type="termsOfAddress">MRT</namePart><affiliation>Departamento de Radiología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cecilia V.</namePart><namePart type="family">Rojas</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Instituto Nutrición y Tecnología Alimentos, Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan</namePart><namePart type="family">Hauke</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eric</namePart><namePart type="family">Hahnen</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rafael</namePart><namePart type="family">González</namePart><namePart type="termsOfAddress">SLP</namePart><affiliation>Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicolas</namePart><namePart type="family">Seleme</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departamento de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Verónica</namePart><namePart type="family">Fernández</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departamento de Ciencias Neurológicas Oriente, Servicio Neuro‐Oftalmología, Universidad de Chile, Santiago, Chile</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexander</namePart><namePart type="family">Schmidt</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ferdinand</namePart><namePart type="family">Binkofski</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Detlef</namePart><namePart type="family">Kömpf</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christian</namePart><namePart type="family">Kubisch</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Human Genetics, University of Cologne, Cologne, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Johann</namePart><namePart type="family">Hagenah</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Klein</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alfredo</namePart><namePart type="family">Ramirez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Luebeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-09-15</dateIssued><dateCaptured encoding="w3cdtf">2008-11-13</dateCaptured><dateValid encoding="w3cdtf">2009-12-11</dateValid><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="tables">2</extent><extent unit="references">24</extent><extent unit="words">6040</extent></physicalDescription><abstract lang="en">We report the clinical features of the original Chilean family with Kufor‐Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile‐onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial‐faucial‐finger minimyoclonus. Neurological and neuropsychological examination during a 10‐year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound‐heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial‐faucial‐finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*‐hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. © 2010 Movement Disorder Society.</abstract><subject lang="en"><genre>Keywords</genre><topic>juvenile Parkinsonism</topic><topic>ATP13A2 mutations</topic><topic>minimyoclonus</topic><topic>saccadic pursuit</topic><topic>DNA methylation</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supporting Video - </note><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1929</start><end>1937</end><total>9</total></extent></part></relatedItem><identifier type="istex">3750C8F32896C3226E71DA44843798B6E1366124</identifier><identifier type="DOI">10.1002/mds.22996</identifier><identifier type="ArticleID">MDS22996</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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