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A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects

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A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects. / Warnecke, Tobias; Duning, Thomas; Schirmacher, Anja; Mohammadi, Siawoosh; Schwindt, Wolfram; Lohmann, Hubertus; Dziewas, Rainer; Deppe, Michael; Ringelstein, E Bernd; Young, Peter.

in: MOVEMENT DISORD, Jahrgang 25, Nr. 4, 15.03.2010, S. 413-20.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Warnecke, T, Duning, T, Schirmacher, A, Mohammadi, S, Schwindt, W, Lohmann, H, Dziewas, R, Deppe, M, Ringelstein, EB & Young, P 2010, 'A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects', MOVEMENT DISORD, Jg. 25, Nr. 4, S. 413-20. https://doi.org/10.1002/mds.22949

APA

Warnecke, T., Duning, T., Schirmacher, A., Mohammadi, S., Schwindt, W., Lohmann, H., Dziewas, R., Deppe, M., Ringelstein, E. B., & Young, P. (2010). A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects. MOVEMENT DISORD, 25(4), 413-20. https://doi.org/10.1002/mds.22949

Vancouver

Warnecke T, Duning T, Schirmacher A, Mohammadi S, Schwindt W, Lohmann H et al. A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects. MOVEMENT DISORD. 2010 Mär 15;25(4):413-20. https://doi.org/10.1002/mds.22949

Bibtex

@article{7e8d5f1cc59c48f592852f04a2895a18,
title = "A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects",
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.",
keywords = "Adult, Amino Acid Substitution, Atrophy, Brain, DNA Mutational Analysis, DNA, Recombinant, Diffusion Magnetic Resonance Imaging, Electrodiagnosis, Female, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Metalloendopeptidases, Middle Aged, Muscle Fibers, Skeletal, Neural Pathways, Neuropsychological Tests, Phenotype, Point Mutation, Spastic Paraplegia, Hereditary, Twins, Dizygotic, Twins, Monozygotic",
author = "Tobias Warnecke and Thomas Duning and Anja Schirmacher and Siawoosh Mohammadi and Wolfram Schwindt and Hubertus Lohmann and Rainer Dziewas and Michael Deppe and Ringelstein, {E Bernd} and Peter Young",
year = "2010",
month = mar,
day = "15",
doi = "10.1002/mds.22949",
language = "English",
volume = "25",
pages = "413--20",
journal = "MOVEMENT DISORD",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects

AU - Warnecke, Tobias

AU - Duning, Thomas

AU - Schirmacher, Anja

AU - Mohammadi, Siawoosh

AU - Schwindt, Wolfram

AU - Lohmann, Hubertus

AU - Dziewas, Rainer

AU - Deppe, Michael

AU - Ringelstein, E Bernd

AU - Young, Peter

PY - 2010/3/15

Y1 - 2010/3/15

N2 - 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.

AB - 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.

KW - Adult

KW - Amino Acid Substitution

KW - Atrophy

KW - Brain

KW - DNA Mutational Analysis

KW - DNA, Recombinant

KW - Diffusion Magnetic Resonance Imaging

KW - Electrodiagnosis

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Testing

KW - Genotype

KW - Humans

KW - Metalloendopeptidases

KW - Middle Aged

KW - Muscle Fibers, Skeletal

KW - Neural Pathways

KW - Neuropsychological Tests

KW - Phenotype

KW - Point Mutation

KW - Spastic Paraplegia, Hereditary

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.1002/mds.22949

DO - 10.1002/mds.22949

M3 - SCORING: Journal article

C2 - 20108356

VL - 25

SP - 413

EP - 420

JO - MOVEMENT DISORD

JF - MOVEMENT DISORD

SN - 0885-3185

IS - 4

ER -