Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia

American Journal of Human Genetics
Ingrid K SvensonDouglas A Marchuk

Abstract

Pure hereditary spastic paraplegia (SPG) type 4 is the most common form of autosomal dominant hereditary SPG, a neurodegenerative disease characterized primarily by hyperreflexia and progressive spasticity of the lower limbs. It is caused by mutations in the gene encoding spastin, a member of the AAA family of ATPases. We have screened the spastin gene for mutations in 15 families consistent with linkage to the spastin gene locus, SPG4, and have identified 11 mutations, 10 of which are novel. Five of the mutations identified are in noninvariant splice-junction sequences. Reverse transcription-PCR analysis of mRNA from patients shows that each of these five mutations results in aberrant splicing. One mutation was found to be "leaky," or partially penetrant; that is, the mutant allele produced both mutant (skipped exon) and wild-type (full-length) transcripts. This phenomenon was reproduced in in vitro splicing experiments, with a minigene splicing-vector construct only in the context of the endogenous splice junctions flanking the splice junctions of the skipped exon. In the absence of endogenous splice junctions, only mutant transcript was detected. The existence of at least one leaky mutation suggests that relatively small dif...Continue Reading

References

Aug 1, 1997·Current Opinion in Neurology·J K Fink
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·J KörkköL Ala-Kokko
Mar 21, 2000·American Journal of Human Genetics·B FontaineA Brice
Mar 4, 2000·Human Molecular Genetics·N FonknechtenJ Hazan
Jul 15, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·C McDermottP Shaw
Oct 20, 2000·European Journal of Human Genetics : EJHG·J BürgerA Reis

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Citations

Jan 9, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Matthew M HimsSusan A Slaugenhaupt
Jul 13, 2004·Neurogenetics·Ingrid K SvensonDouglas A Marchuk
Oct 3, 2003·Biochemical and Biophysical Research Communications·Sylvia L AndersonBerish Y Rubin
Aug 7, 2002·Journal of the Neurological Sciences·Christos ProukakisAndrew H Crosby
May 23, 2002·Neuroscience Letters·Mitsuya MoritaRobert H Brown
May 29, 2012·The Journal of Biological Chemistry·Thomas EckertGünther Woehlke
Aug 9, 2011·Human Molecular Genetics·Ranjit S ShettySusan A Slaugenhaupt
Jun 11, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Philip M BooneJames R Lupski
May 6, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Carol J GallioneDouglas A Marchuk
Oct 6, 2007·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J SchickelC Beetz
May 25, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S KlimpeA U Mannan
Jul 23, 2013·PloS One·Doan Tuong-Van LeGünther Woehlke
Feb 29, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joanna M SolowskaPeter W Baas
Sep 11, 2012·Neuroscience Letters·L NanettiC Mariotti
Oct 31, 2009·Journal of the Neurological Sciences·Angela MagarielloAldo Quattrone
Jul 26, 2015·Journal of the Neurological Sciences·Hyunwoong ParkMoon-Woo Seong
May 29, 2007·Biochemical and Biophysical Research Communications·Yuka Matsushita-IshiodoriTeru Ogura
Jun 16, 2004·Movement Disorders : Official Journal of the Movement Disorder Society·Anthony P NicholasRussell L Margolis
Jan 15, 2008·Clinical Genetics·D V K PantakaniA U Mannan
Sep 18, 2007·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·S GeniniP Vögeli
Oct 13, 2005·Journal of Neurochemistry·Sara SalinasThomas T Warner
Jul 11, 2006·American Journal of Human Genetics·Ashraf U MannanWolfgang Engel
May 19, 2004·Biochemical and Biophysical Research Communications·Christian BeetzJörg Schickel
Jun 6, 2003·Biochemical and Biophysical Research Communications·Sylvia L AndersonBerish Y Rubin
Nov 13, 2001·American Journal of Human Genetics·I K SvensonD A Marchuk

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