Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course.
Identifieur interne : 000D74 ( Main/Exploration ); précédent : 000D73; suivant : 000D75Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course.
Auteurs : Núria Set Salvia [Espagne] ; Javier Pagonabarraga ; Henry Houlden ; Berta Pascual-Sedano ; Oriol Dols-Icardo ; Arianna Tucci ; Coro Paisán-Ruiz ; Antonia Campolongo ; Sofía Ant N-Aguirre ; Inés Martín ; Laia Mu Oz ; Enric Bufill ; Lluïsa Vilageliu ; Daniel Grinberg ; M Nica Cozar ; Rafael Blesa ; Alberto Lle ; John Hardy ; Jaime Kulisevsky ; Jordi Clarim NSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2012.
English descriptors
- KwdEn :
- Adult, Aged, Analysis of Variance, Chi-Square Distribution, DNA Mutational Analysis, Disease Progression, Female, Genetic Predisposition to Disease (genetics), Genotype, Glucosylceramidase (genetics), Humans, Lewy Body Disease (complications), Lewy Body Disease (genetics), Male, Middle Aged, Mutation (genetics), Neuropsychological Tests, Parkinsonian Disorders (complications), Parkinsonian Disorders (genetics), Risk Factors.
- MESH :
- chemical , genetics : Glucosylceramidase.
- complications : Lewy Body Disease, Parkinsonian Disorders.
- genetics : Genetic Predisposition to Disease, Lewy Body Disease, Mutation, Parkinsonian Disorders.
- Adult, Aged, Analysis of Variance, Chi-Square Distribution, DNA Mutational Analysis, Disease Progression, Female, Genotype, Humans, Male, Middle Aged, Neuropsychological Tests, Risk Factors.
Abstract
Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia.
DOI: 10.1002/mds.24045
PubMed: 22173904
Affiliations:
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Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Pagonabarraga, Javier" sort="Pagonabarraga, Javier" uniqKey="Pagonabarraga J" first="Javier" last="Pagonabarraga">Javier Pagonabarraga</name></author><author><name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name></author><author><name sortKey="Pascual Sedano, Berta" sort="Pascual Sedano, Berta" uniqKey="Pascual Sedano B" first="Berta" last="Pascual-Sedano">Berta Pascual-Sedano</name></author><author><name sortKey="Dols Icardo, Oriol" sort="Dols Icardo, Oriol" uniqKey="Dols Icardo O" first="Oriol" last="Dols-Icardo">Oriol Dols-Icardo</name></author><author><name sortKey="Tucci, Arianna" sort="Tucci, Arianna" uniqKey="Tucci A" first="Arianna" last="Tucci">Arianna Tucci</name></author><author><name sortKey="Paisan Ruiz, Coro" sort="Paisan Ruiz, Coro" uniqKey="Paisan Ruiz C" first="Coro" last="Paisán-Ruiz">Coro Paisán-Ruiz</name></author><author><name sortKey="Campolongo, Antonia" sort="Campolongo, Antonia" uniqKey="Campolongo A" first="Antonia" last="Campolongo">Antonia Campolongo</name></author><author><name sortKey="Ant N Aguirre, Sofia" sort="Ant N Aguirre, Sofia" uniqKey="Ant N Aguirre S" first="Sofía" last="Ant N-Aguirre">Sofía Ant N-Aguirre</name></author><author><name sortKey="Martin, Ines" sort="Martin, Ines" uniqKey="Martin I" first="Inés" last="Martín">Inés Martín</name></author><author><name sortKey="Mu Oz, Laia" sort="Mu Oz, Laia" uniqKey="Mu Oz L" first="Laia" last="Mu Oz">Laia Mu Oz</name></author><author><name sortKey="Bufill, Enric" sort="Bufill, Enric" uniqKey="Bufill E" first="Enric" last="Bufill">Enric Bufill</name></author><author><name sortKey="Vilageliu, Lluisa" sort="Vilageliu, Lluisa" uniqKey="Vilageliu L" first="Lluïsa" last="Vilageliu">Lluïsa Vilageliu</name></author><author><name sortKey="Grinberg, Daniel" sort="Grinberg, Daniel" uniqKey="Grinberg D" first="Daniel" last="Grinberg">Daniel Grinberg</name></author><author><name sortKey="Cozar, M Nica" sort="Cozar, M Nica" uniqKey="Cozar M" first="M Nica" last="Cozar">M Nica Cozar</name></author><author><name sortKey="Blesa, Rafael" sort="Blesa, Rafael" uniqKey="Blesa R" first="Rafael" last="Blesa">Rafael Blesa</name></author><author><name sortKey="Lle, Alberto" sort="Lle, Alberto" uniqKey="Lle A" first="Alberto" last="Lle">Alberto Lle</name></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name></author><author><name sortKey="Kulisevsky, Jaime" sort="Kulisevsky, Jaime" uniqKey="Kulisevsky J" first="Jaime" last="Kulisevsky">Jaime Kulisevsky</name></author><author><name sortKey="Clarim N, Jordi" sort="Clarim N, Jordi" uniqKey="Clarim N J" first="Jordi" last="Clarim N">Jordi Clarim N</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Analysis of Variance</term><term>Chi-Square Distribution</term><term>DNA Mutational Analysis</term><term>Disease Progression</term><term>Female</term><term>Genetic Predisposition to Disease (genetics)</term><term>Genotype</term><term>Glucosylceramidase (genetics)</term><term>Humans</term><term>Lewy Body Disease (complications)</term><term>Lewy Body Disease (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation (genetics)</term><term>Neuropsychological Tests</term><term>Parkinsonian Disorders (complications)</term><term>Parkinsonian Disorders (genetics)</term><term>Risk Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glucosylceramidase</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Lewy Body Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term><term>Lewy Body Disease</term><term>Mutation</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Analysis of Variance</term><term>Chi-Square Distribution</term><term>DNA Mutational Analysis</term><term>Disease Progression</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Risk Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia.</div></front></TEI><affiliations><list><country><li>Espagne</li></country><region><li>Catalogne</li></region><settlement><li>Barcelone</li></settlement><orgName><li>Université autonome de Barcelone</li></orgName></list><tree><noCountry><name sortKey="Ant N Aguirre, Sofia" sort="Ant N Aguirre, Sofia" uniqKey="Ant N Aguirre S" first="Sofía" last="Ant N-Aguirre">Sofía Ant N-Aguirre</name><name sortKey="Blesa, Rafael" sort="Blesa, Rafael" uniqKey="Blesa R" first="Rafael" last="Blesa">Rafael Blesa</name><name sortKey="Bufill, Enric" sort="Bufill, Enric" uniqKey="Bufill E" first="Enric" last="Bufill">Enric Bufill</name><name sortKey="Campolongo, Antonia" sort="Campolongo, Antonia" uniqKey="Campolongo A" first="Antonia" last="Campolongo">Antonia Campolongo</name><name sortKey="Clarim N, Jordi" sort="Clarim N, Jordi" uniqKey="Clarim N J" first="Jordi" last="Clarim N">Jordi Clarim N</name><name sortKey="Cozar, M Nica" sort="Cozar, M Nica" uniqKey="Cozar M" first="M Nica" last="Cozar">M Nica Cozar</name><name sortKey="Dols Icardo, Oriol" sort="Dols Icardo, Oriol" uniqKey="Dols Icardo O" first="Oriol" last="Dols-Icardo">Oriol Dols-Icardo</name><name sortKey="Grinberg, Daniel" sort="Grinberg, Daniel" uniqKey="Grinberg D" first="Daniel" last="Grinberg">Daniel Grinberg</name><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name><name sortKey="Kulisevsky, Jaime" sort="Kulisevsky, Jaime" uniqKey="Kulisevsky J" first="Jaime" last="Kulisevsky">Jaime Kulisevsky</name><name sortKey="Lle, Alberto" sort="Lle, Alberto" uniqKey="Lle A" first="Alberto" last="Lle">Alberto Lle</name><name sortKey="Martin, Ines" sort="Martin, Ines" uniqKey="Martin I" first="Inés" last="Martín">Inés Martín</name><name sortKey="Mu Oz, Laia" sort="Mu Oz, Laia" uniqKey="Mu Oz L" first="Laia" last="Mu Oz">Laia Mu Oz</name><name sortKey="Pagonabarraga, Javier" sort="Pagonabarraga, Javier" uniqKey="Pagonabarraga J" first="Javier" last="Pagonabarraga">Javier Pagonabarraga</name><name sortKey="Paisan Ruiz, Coro" sort="Paisan Ruiz, Coro" uniqKey="Paisan Ruiz C" first="Coro" last="Paisán-Ruiz">Coro Paisán-Ruiz</name><name sortKey="Pascual Sedano, Berta" sort="Pascual Sedano, Berta" uniqKey="Pascual Sedano B" first="Berta" last="Pascual-Sedano">Berta Pascual-Sedano</name><name sortKey="Tucci, Arianna" sort="Tucci, Arianna" uniqKey="Tucci A" first="Arianna" last="Tucci">Arianna Tucci</name><name sortKey="Vilageliu, Lluisa" sort="Vilageliu, Lluisa" uniqKey="Vilageliu L" first="Lluïsa" last="Vilageliu">Lluïsa Vilageliu</name></noCountry><country name="Espagne"><region name="Catalogne"><name sortKey="Set Salvia, Nuria" sort="Set Salvia, Nuria" uniqKey="Set Salvia N" first="Núria" last="Set Salvia">Núria Set Salvia</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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