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CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A

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@article{55b16e9fc0f1488ba554ff7bd5d04460,
title = "CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A",
abstract = "UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described.OBJECTIVE: This study characterizes four unrelated SPG5A patients through clinical evaluation.METHODS: The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy.RESULTS: One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA).CONCLUSION: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.",
keywords = "Adolescent, Adult, Brain, Cohort Studies, DNA Mutational Analysis, Evoked Potentials, Motor, Evoked Potentials, Somatosensory, Female, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Middle Aged, Mutation, Nerve Fibers, Myelinated, Neural Conduction, Spastic Paraplegia, Hereditary, Steroid Hydroxylases, Young Adult",
author = "Peter Roos and K Svenstrup and Danielsen, {E R} and C Thomsen and Nielsen, {J{\o}rgen Erik}",
note = "{\circledC} 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2014",
month = "5",
doi = "10.1111/ane.12188",
language = "English",
volume = "129",
pages = "330--4",
journal = "Acta Neurologica Scandinavica",
issn = "0001-6314",
publisher = "Wiley-Blackwell Munksgaard",
number = "5",

}

RIS

TY - JOUR

T1 - CYP7B1

T2 - novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A

AU - Roos, Peter

AU - Svenstrup, K

AU - Danielsen, E R

AU - Thomsen, C

AU - Nielsen, Jørgen Erik

N1 - © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/5

Y1 - 2014/5

N2 - UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described.OBJECTIVE: This study characterizes four unrelated SPG5A patients through clinical evaluation.METHODS: The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy.RESULTS: One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA).CONCLUSION: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.

AB - UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described.OBJECTIVE: This study characterizes four unrelated SPG5A patients through clinical evaluation.METHODS: The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy.RESULTS: One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA).CONCLUSION: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.

KW - Adolescent

KW - Adult

KW - Brain

KW - Cohort Studies

KW - DNA Mutational Analysis

KW - Evoked Potentials, Motor

KW - Evoked Potentials, Somatosensory

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging

KW - Magnetic Resonance Spectroscopy

KW - Middle Aged

KW - Mutation

KW - Nerve Fibers, Myelinated

KW - Neural Conduction

KW - Spastic Paraplegia, Hereditary

KW - Steroid Hydroxylases

KW - Young Adult

U2 - 10.1111/ane.12188

DO - 10.1111/ane.12188

M3 - Journal article

VL - 129

SP - 330

EP - 334

JO - Acta Neurologica Scandinavica

JF - Acta Neurologica Scandinavica

SN - 0001-6314

IS - 5

ER -

ID: 44892458