Diffusion Tensor Imaging in Male Premutation Carriers of the Fragile X Mental Retardation Gene
Identifieur interne : 000631 ( PascalFrancis/Checkpoint ); précédent : 000630; suivant : 000632Diffusion Tensor Imaging in Male Premutation Carriers of the Fragile X Mental Retardation Gene
Auteurs : Ryu-Ichiro Hashimoto [États-Unis] ; Siddharth Srivastava [États-Unis] ; Flora Tassone [États-Unis] ; Randi J. Hagerman [États-Unis] ; Susan M. Rivera [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2011.
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Abstract
Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X-associated tremor/ataxia syndrome and healthy sex-matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar-brain stem and limbic systems. Compared with healthy controls, patients with fragile X-associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel-wise analysis using tract-based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X-associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U-shaped relationship between CGG-repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar-brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology.
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Hagerman</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Medical Investigation of Neurodevelopmental Disorder (MIND), University of California, Davis</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Pediatrics, University of California, Davis Medical Center</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Rivera, Susan M" sort="Rivera, Susan M" uniqKey="Rivera S" first="Susan M." last="Rivera">Susan M. Rivera</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Mind and Brain, University of California, Davis</s1><s2>Davis, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Medical Investigation of Neurodevelopmental Disorder (MIND), University of California, Davis</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Psychology, University of California, Davis</s1><s2>Davis, California</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Carrier</term><term>Cerebellum</term><term>Diffusion tensor imaging</term><term>Fragile X syndrome</term><term>Fragile X-associated tremor/ataxia syndrome</term><term>Mental retardation</term><term>Nervous system diseases</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Syndrome du chromosome X fragile</term><term>Arriération mentale</term><term>Pathologie du système nerveux</term><term>Imagerie du tenseur de diffusion</term><term>Porteur</term><term>Cervelet</term><term>Syndrome des tremblements ataxiques associé au X fragile</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X-associated tremor/ataxia syndrome and healthy sex-matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar-brain stem and limbic systems. Compared with healthy controls, patients with fragile X-associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel-wise analysis using tract-based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X-associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U-shaped relationship between CGG-repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar-brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>26</s2></fA05><fA06><s2>7</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Diffusion Tensor Imaging in Male Premutation Carriers of the Fragile X Mental Retardation Gene</s1></fA08><fA11 i1="01" i2="1"><s1>HASHIMOTO (Ryu-Ichiro)</s1></fA11><fA11 i1="02" i2="1"><s1>SRIVASTAVA (Siddharth)</s1></fA11><fA11 i1="03" i2="1"><s1>TASSONE (Flora)</s1></fA11><fA11 i1="04" i2="1"><s1>HAGERMAN (Randi J.)</s1></fA11><fA11 i1="05" i2="1"><s1>RIVERA (Susan M.)</s1></fA11><fA14 i1="01"><s1>Center for Mind and Brain, University of California, Davis</s1><s2>Davis, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="02"><s1>Medical Investigation of Neurodevelopmental Disorder (MIND), University of California, Davis</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Biochemistry and Molecular Medicine, University of California, Davis</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Pediatrics, University of California, Davis Medical Center</s1><s2>Sacramento, California</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Psychology, University of California, Davis</s1><s2>Davis, California</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA20><s1>1329-1336</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000190480410200</s5></fA43><fA44><s0>0000</s0><s1>© 2011 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>37 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>11-0321220</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X-associated tremor/ataxia syndrome and healthy sex-matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar-brain stem and limbic systems. Compared with healthy controls, patients with fragile X-associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel-wise analysis using tract-based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X-associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U-shaped relationship between CGG-repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar-brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B24A06</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Syndrome du chromosome X fragile</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Fragile X syndrome</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>X frágil síndrome</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Arriération mentale</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Mental retardation</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Retraso mental</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Imagerie du tenseur de diffusion</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Diffusion tensor imaging</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Imágen de tensor de difusión</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Porteur</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Carrier</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Portador</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Cervelet</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Cerebellum</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Cerebelo</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Syndrome des tremblements ataxiques associé au X fragile</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Fragile X-associated tremor/ataxia syndrome</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Síndrome de temblor y ataxía asociados a premutación X- frágil</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Fragilité chromosomique</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Chromosome fragility</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Fragilidad cromosómica</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Déficience intellectuelle</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Intellectual deficiency</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Deficiencia intelectual</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Trouble du développement</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Developmental disorder</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Trastorno desarrollo</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Encéphale</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Encephalon</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Encéfalo</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervioso central</s0><s5>41</s5></fC07><fN21><s1>220</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Hashimoto, Ryu Ichiro" sort="Hashimoto, Ryu Ichiro" uniqKey="Hashimoto R" first="Ryu-Ichiro" last="Hashimoto">Ryu-Ichiro Hashimoto</name></region><name sortKey="Hagerman, Randi J" sort="Hagerman, Randi J" uniqKey="Hagerman R" first="Randi J." last="Hagerman">Randi J. Hagerman</name><name sortKey="Hagerman, Randi J" sort="Hagerman, Randi J" uniqKey="Hagerman R" first="Randi J." last="Hagerman">Randi J. Hagerman</name><name sortKey="Rivera, Susan M" sort="Rivera, Susan M" uniqKey="Rivera S" first="Susan M." last="Rivera">Susan M. Rivera</name><name sortKey="Rivera, Susan M" sort="Rivera, Susan M" uniqKey="Rivera S" first="Susan M." last="Rivera">Susan M. Rivera</name><name sortKey="Rivera, Susan M" sort="Rivera, Susan M" uniqKey="Rivera S" first="Susan M." last="Rivera">Susan M. Rivera</name><name sortKey="Srivastava, Siddharth" sort="Srivastava, Siddharth" uniqKey="Srivastava S" first="Siddharth" last="Srivastava">Siddharth Srivastava</name><name sortKey="Tassone, Flora" sort="Tassone, Flora" uniqKey="Tassone F" first="Flora" last="Tassone">Flora Tassone</name><name sortKey="Tassone, Flora" sort="Tassone, Flora" uniqKey="Tassone F" first="Flora" last="Tassone">Flora Tassone</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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