MovDisordV3, Main, Merge, bibRecord, 002820

A Novel Splice Site Mutation in the SPG7 Gene Causing Widespread Fiber Damage in Homozygous and Heterozygous Subjects

Identifieur interne : 002820 ( Main/Merge ); précédent : 002819; suivant : 002821

A Novel Splice Site Mutation in the SPG7 Gene Causing Widespread Fiber Damage in Homozygous and Heterozygous Subjects

Auteurs : Tobias Warnecke [Allemagne] ; Thomas Duning [Allemagne] ; Anja Schirmacher [Allemagne] ; Siawoosh Mohammadi [Allemagne] ; Wolfram Schwindt [Allemagne] ; Hubertus Lohmann [Allemagne] ; Rainer Dziewas [Allemagne] ; Michael Deppe [Allemagne] ; E. Bernd Ringelstein [Allemagne] ; Peter Young [Allemagne]

Source :

Movement disorders [ 0885-3185 ] ; 2010.

RBID : Pascal:10-0178211

Descripteurs français

Pascal (Inist)
- Paraplégie spasmodique héréditaire de Strümpell-Lorrain, Pathologie du système nerveux, Epissage, Epissure, Mutation, Homozygotie, Homme, Substance blanche, Imagerie du tenseur de diffusion.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Diffusion tensor imaging, Hereditary spastic paraplegia, Homozygosity, Human, Mutation, Nervous system diseases, Splice, Splicing, White matter.

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.

Links toward previous steps (curation, corpus...)

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Links to Exploration step

Pascal:10-0178211

Le document en format XML

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<term>Hereditary spastic paraplegia</term>
<term>Homozygosity</term>
<term>Human</term>
<term>Mutation</term>
<term>Nervous system diseases</term>
<term>Splice</term>
<term>Splicing</term>
<term>White matter</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Paraplégie spasmodique héréditaire de Strümpell-Lorrain</term>
<term>Pathologie du   système nerveux</term>
<term>Epissage</term>
<term>Epissure</term>
<term>Mutation</term>
<term>Homozygotie</term>
<term>Homme</term>
<term>Substance blanche</term>
<term>Imagerie du tenseur de diffusion</term>
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<front><div type="abstract" xml: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.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>District de Münster</li>
<li>Rhénanie-du-Nord-Westphalie</li>
</region>
<settlement><li>Münster</li>
</settlement>
</list>
<tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Warnecke, Tobias" sort="Warnecke, Tobias" uniqKey="Warnecke T" first="Tobias" last="Warnecke">Tobias Warnecke</name>
</region>
<name sortKey="Bernd Ringelstein, E" sort="Bernd Ringelstein, E" uniqKey="Bernd Ringelstein E" first="E." last="Bernd Ringelstein">E. Bernd Ringelstein</name>
<name sortKey="Deppe, Michael" sort="Deppe, Michael" uniqKey="Deppe M" first="Michael" last="Deppe">Michael Deppe</name>
<name sortKey="Duning, Thomas" sort="Duning, Thomas" uniqKey="Duning T" first="Thomas" last="Duning">Thomas Duning</name>
<name sortKey="Dziewas, Rainer" sort="Dziewas, Rainer" uniqKey="Dziewas R" first="Rainer" last="Dziewas">Rainer Dziewas</name>
<name sortKey="Lohmann, Hubertus" sort="Lohmann, Hubertus" uniqKey="Lohmann H" first="Hubertus" last="Lohmann">Hubertus Lohmann</name>
<name sortKey="Mohammadi, Siawoosh" sort="Mohammadi, Siawoosh" uniqKey="Mohammadi S" first="Siawoosh" last="Mohammadi">Siawoosh Mohammadi</name>
<name sortKey="Schirmacher, Anja" sort="Schirmacher, Anja" uniqKey="Schirmacher A" first="Anja" last="Schirmacher">Anja Schirmacher</name>
<name sortKey="Schwindt, Wolfram" sort="Schwindt, Wolfram" uniqKey="Schwindt W" first="Wolfram" last="Schwindt">Wolfram Schwindt</name>
<name sortKey="Young, Peter" sort="Young, Peter" uniqKey="Young P" first="Peter" last="Young">Peter Young</name>
</country>
</tree>
</affiliations>
</record>

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	Movement Disorders (revue)
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Movement Disorders (revue)

A Novel Splice Site Mutation in the SPG7 Gene Causing Widespread Fiber Damage in Homozygous and Heterozygous Subjects

A Novel Splice Site Mutation in the SPG7 Gene Causing Widespread Fiber Damage in Homozygous and Heterozygous Subjects

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