A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects
Identifieur interne : 000465 ( Istex/Corpus ); précédent : 000464; suivant : 000466A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects
Auteurs : Tobias Warnecke ; Thomas Duning ; Anja Schirmacher ; Siawoosh Mohammadi ; Wolfram Schwindt ; Hubertus Lohmann ; Rainer Dziewas ; Michael Deppe ; E. Bernd Ringelstein ; Peter YoungSource :
- Movement Disorders [ 0885-3185 ] ; 2010-03-15.
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- KwdEn :
Abstract
Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society
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DOI: 10.1002/mds.22949
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ISTEX:4E0DADD9E2EFDCDD209819A76B6EBC055BB6468ALe document en format XML
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The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Tobias Warnecke MD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Thomas Duning MD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Anja Schirmacher PhD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Siawoosh Mohammadi PhD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Wolfram Schwindt MD</name><affiliations><json:string>Department of Clinical Radiology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Hubertus Lohmann PhD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Rainer Dziewas MD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Michael Deppe PhD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>E. Bernd Ringelstein MD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item><json:item><name>Peter Young MD</name><affiliations><json:string>Department of Neurology, University Hospital of Münster, Münster, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>hereditary spastic paraplegia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SPG7</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>splice site mutation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>white matter damage</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>diffusion tensor imaging</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society</abstract><qualityIndicators><score>7.544</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1739</abstractCharCount><pdfWordCount>4544</pdfWordCount><pdfCharCount>29643</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>255</abstractWordCount></qualityIndicators><title>A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects</title><genre><json:string>Serial article</json:string></genre><host><volume>25</volume><pages><total>8</total><last>420</last><first>413</first></pages><issn><json:string>0885-3185</json:string></issn><issue>4</issue><subject><json:item><value>Research 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xml:lang="en">A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Wiley Subscription Services, Inc., A Wiley Company</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects</title><author><persName><forename type="first">Tobias</forename><surname>Warnecke</surname><roleName type="degree">MD</roleName></persName><note type="biography">The first two authors contributed equally to this work.</note><affiliation>The first two authors contributed equally to this work.</affiliation><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Duning</surname><roleName type="degree">MD</roleName></persName><note type="biography">The first two authors contributed equally to this work.</note><affiliation>The first two authors contributed equally to this work.</affiliation><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Anja</forename><surname>Schirmacher</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Siawoosh</forename><surname>Mohammadi</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Wolfram</forename><surname>Schwindt</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Clinical Radiology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Hubertus</forename><surname>Lohmann</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Rainer</forename><surname>Dziewas</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Michael</forename><surname>Deppe</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">E. Bernd</forename><surname>Ringelstein</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Young</surname><roleName type="degree">MD</roleName></persName><note type="correspondence"><p>Correspondence: Department of Neurology, University Hospital of Münster, Albert‐Schweitzer‐Strasse 33, 48129 Münster, Germany</p></note><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-03-15"></date><biblScope unit="vol">25</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="413">413</biblScope><biblScope unit="page" to="420">420</biblScope></imprint></monogr><idno type="istex">4E0DADD9E2EFDCDD209819A76B6EBC055BB6468A</idno><idno type="DOI">10.1002/mds.22949</idno><idno type="ArticleID">MDS22949</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>hereditary spastic paraplegia</term></item><item><term>SPG7</term></item><item><term>splice site mutation</term></item><item><term>white matter damage</term></item><item><term>diffusion tensor imaging</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="2009-09-23">Received</change><change when="2009-11-12">Registration</change><change when="2010-03-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/4E0DADD9E2EFDCDD209819A76B6EBC055BB6468A/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. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/mds.v25:4</doi><numberingGroup><numbering type="journalVolume" number="25">25</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="2010-03-15">15 March 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="30" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.22949</doi><idGroup><id type="unit" value="MDS22949"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2009-09-23"></event><event type="manuscriptRevised" date="2009-11-04"></event><event type="manuscriptAccepted" date="2009-11-12"></event><event type="firstOnline" date="2010-01-27"></event><event type="publishedOnlineFinalForm" date="2010-03-16"></event><event type="publishedOnlineAcceptedOrEarlyUnpaginated" date="2010-01-27"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.5.2 mode:FullText" date="2011-08-12"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">413</numbering><numbering type="pageLast">420</numbering></numberingGroup><correspondenceTo>Department of Neurology, University Hospital of Münster, Albert‐Schweitzer‐Strasse 33, 48129 Münster, Germany</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS22949.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="43"></count><count type="wordTotal" number="4764"></count></countGroup><titleGroup><title type="main" xml:lang="en">A novel splice site mutation in the <i>SPG7</i> gene causing widespread fiber damage in homozygous and heterozygous subjects<link href="#fn1"></link></title><title type="short" xml:lang="en">A Novel Splice Site Mutation in the SPG7 Gene</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" noteRef="#fn2"><personName><givenNames>Tobias</givenNames><familyName>Warnecke</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1" noteRef="#fn2"><personName><givenNames>Thomas</givenNames><familyName>Duning</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Anja</givenNames><familyName>Schirmacher</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Siawoosh</givenNames><familyName>Mohammadi</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Wolfram</givenNames><familyName>Schwindt</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Hubertus</givenNames><familyName>Lohmann</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Rainer</givenNames><familyName>Dziewas</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael</givenNames><familyName>Deppe</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>E. Bernd</givenNames><familyName>Ringelstein</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Peter</givenNames><familyName>Young</familyName><degrees>MD</degrees></personName><contactDetails><email normalForm="young@uni-muenster.de">young@uni‐muenster.de</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Department of Clinical Radiology, University Hospital of Münster, Münster, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">hereditary spastic paraplegia</keyword><keyword xml:id="kwd2"><i>SPG7</i></keyword><keyword xml:id="kwd3">splice site mutation</keyword><keyword xml:id="kwd4">white matter damage</keyword><keyword xml:id="kwd5">diffusion tensor imaging</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of <i>SPG4</i> and <i>SPG7</i> gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the <i>SPG7</i> gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the <i>SPG7</i> gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for <i>SPG7</i>‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: Nothing to report.</p></note><note xml:id="fn2"><p>The first two authors contributed equally to this work.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>A Novel Splice Site Mutation in the SPG7 Gene</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A novel splice site mutation in the</title></titleInfo><name type="personal"><namePart type="given">Tobias</namePart><namePart type="family">Warnecke</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><description>The first two authors contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Duning</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><description>The first two authors contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anja</namePart><namePart type="family">Schirmacher</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Siawoosh</namePart><namePart type="family">Mohammadi</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wolfram</namePart><namePart type="family">Schwindt</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Clinical Radiology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hubertus</namePart><namePart type="family">Lohmann</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rainer</namePart><namePart type="family">Dziewas</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Deppe</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E. Bernd</namePart><namePart type="family">Ringelstein</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Young</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University Hospital of Münster, Münster, Germany</affiliation><description>Correspondence: Department of Neurology, University Hospital of Münster, Albert‐Schweitzer‐Strasse 33, 48129 Münster, Germany</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-03-15</dateIssued><dateCaptured encoding="w3cdtf">2009-09-23</dateCaptured><dateValid encoding="w3cdtf">2009-11-12</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="references">43</extent><extent unit="words">4764</extent></physicalDescription><abstract lang="en">Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><subject lang="en"><genre>Keywords</genre><topic>hereditary spastic paraplegia</topic><topic>SPG7</topic><topic>splice site mutation</topic><topic>white matter damage</topic><topic>diffusion tensor imaging</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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