Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurogenetics
Published in: neurogenetics 2/2009

01-04-2009 | Original Article

Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia

Authors: Rebecca Schüle, Elisabeth Brandt, Kathrin N. Karle, Maria Tsaousidou, Stephan Klebe, Sven Klimpe, Michaela Auer-Grumbach, Andrew H. Crosby, Christian A. Hübner, Ludger Schöls, Thomas Deufel, Christian Beetz

Published in: Neurogenetics | Issue 2/2009

Login to get access

Abstract

Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations.
Appendix
Available only for authorised users
Literature
1.
2.
Depienne C, Stevanin G, Brice A, Durr A (2007) Hereditary spastic paraplegias: an update. Curr Opin Neurol 20:674–680CrossRefPubMed
3.
Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH (2008) Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet 82:510–515, doi:10.​1016/​j.​ajhg.​2007.​10.​001 CrossRefPubMed
4.
Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, Hamri A, Benomar A, Lossos A, Denora P, Fernandez J, Elleuch N, Forlani S, Durr A, Feki I, Hutchinson M, Santorelli FM, Mhiri C, Brice A, Stevanin G (2008) Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet 82:992–1002, doi:10.​1016/​j.​ajhg.​2008.​03.​004 CrossRefPubMed
5.
Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, De Michele G, Filla A, Cocozza S, Marconi R, Durr A, Fontaine B, Ballabio A (1998) Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93:973–983, doi:10.​1016/​S0092-8674(00)81203-9 CrossRefPubMed
6.
Fonknechten N, Mavel D, Byrne P, Davoine CS, Cruaud C, Bonsch D, Samson D, Coutinho P, Hutchinson M, McMonagle P, Burgunder JM, Tartaglione A, Heinzlef O, Feki I, Deufel T, Parfrey N, Brice A, Fontaine B, Prud'homme JF, Weissenbach J, Durr A, Hazan J (2000) Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Hum Mol Genet 9:637–644, doi:10.​1093/​hmg/​9.​4.​637 CrossRefPubMed
7.
Sauter SM, Engel W, Neumann LM, Kunze J, Neesen J (2004) Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus. Hum Mutat 23:98, doi:10.​1002/​humu.​9205 CrossRefPubMed
8.
Beetz C, Schule R, Deconinck T, Tran-Viet KN, Zhu H, Kremer BP, Frints SG, van Zelst-Stams WA, Byrne P, Otto S, Nygren AO, Baets J, Smets K, Ceulemans B, Dan B, Nagan N, Kassubek J, Klimpe S, Klopstock T, Stolze H, Smeets HJ, Schrander-Stumpel CT, Hutchinson M, van de Warrenburg BP, Braastad C, Deufel T, Pericak-Vance M, Schols L, de Jonghe P, Zuchner S (2008) REEP1 mutation spectrum and genotype/phenotype correlation in hereditary spastic paraplegia type 31. Brain 131:1078–1086, doi:10.​1093/​brain/​awn026 CrossRefPubMed
9.
Hentati A, Pericak-Vance MA, Hung WY, Belal S, Laing N, Boustany RM, Hentati F, Ben Hamida M, Siddique T (1994) Linkage of ‘pure’ autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic locus heterogeneity. Hum Mol Genet 3:1263–1267, doi:10.​1093/​hmg/​3.​8.​1263 CrossRefPubMed
10.
Klebe S, Durr A, Bouslam N, Grid D, Paternotte C, Depienne C, Hanein S, Bouhouche A, Elleuch N, Azzedine H, Poea-Guyon S, Forlani S, Denis E, Charon C, Hazan J, Brice A, Stevanin G (2007) Spastic paraplegia 5: locus refinement, candidate gene analysis and clinical description. Am J Med Genet B Neuropsychiatr Genet 144B:854–861, doi:10.​1002/​ajmg.​b.​30518 CrossRefPubMed
11.
Coutinho P, Barros J, Zemmouri R, Guimaraes J, Alves C, Chorao R, Lourenco E, Ribeiro P, Loureiro JL, Santos JV, Hamri A, Paternotte C, Hazan J, Silva MC, Prud'homme JF, Grid D (1999) Clinical heterogeneity of autosomal recessive spastic paraplegias: analysis of 106 patients in 46 families. Arch Neurol 56:943–949, doi:10.​1001/​archneur.​56.​8.​943 CrossRefPubMed
12.
Wilkinson PA, Crosby AH, Turner C, Patel H, Wood NW, Schapira AH, Warner TT (2003) A clinical and genetic study of SPG5A linked autosomal recessive hereditary spastic paraplegia. Neurology 61:235–238PubMed
13.
Muglia M, Criscuolo C, Magariello A, De Michele G, Scarano V, D'Adamo P, Ambrosio G, Gabriele AL, Patitucci A, Mazzei R, Conforti FL, Sprovieri T, Morgante L, Epifanio A, La Spina P, Valentino P, Gasparini P, Filla A, Quattrone A (2004) Narrowing of the critical region in autosomal recessive spastic paraplegia linked to the SPG5 locus. Neurogenetics 5:49–54, doi:10.​1007/​s10048-003-0167-7 CrossRefPubMed
14.
Beetz C, Nygren AO, Schickel J, Auer-Grumbach M, Burk K, Heide G, Kassubek J, Klimpe S, Klopstock T, Kreuz F, Otto S, Schule R, Schols L, Sperfeld AD, Witte OW, Deufel T (2006) High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia. Neurology 67:1926–1930, doi:10.​1212/​01.​wnl.​0000244413.​49258.​f5 CrossRefPubMed
15.
16.
Beetz C, Schule R, Klebe S, Klimpe S, Klopstock T, Lacour A, Otto S, Sperfeld AD, van de Warrenburg B, Schols L, Deufel T (2008) Screening of hereditary spastic paraplegia patients for alterations at NIPA1 mutational hotspots. J Neurol Sci 268:131–135, doi:10.​1016/​j.​jns.​2007.​11.​015 CrossRefPubMed
17.
18.
Arnoldi A, Tonelli A, Crippa F, Villani G, Pacelli C, Sironi M, Pozzoli U, D'Angelo MG, Meola G, Martinuzzi A, Crimella C, Redaelli F, Panzeri C, Renieri A, Comi GP, Turconi AC, Bresolin N, Bassi MT (2008) A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. Hum Mutat 29:522–531, doi:10.​1002/​humu.​20682 CrossRefPubMed
19.
Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, Rosa AL, Lerer I, Hamri A, Alegria P, Loureiro J, Tada M, Hannequin D, Anheim M, Goizet C, Gonzalez-Martinez V, Le Ber I, Forlani S, Iwabuchi K, Meiner V, Uyanik G, Erichsen AK, Feki I, Pasquier F, Belarbi S, Cruz VT, Depienne C, Truchetto J, Garrigues G, Tallaksen C, Tranchant C, Nishizawa M, Vale J, Coutinho P, Santorelli FM, Mhiri C, Brice A, Durr A (2008) Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain 131:772–784, doi:10.​1093/​brain/​awm293 CrossRefPubMed
20.
Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribai P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, Brice A (2007) Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. J Med Genet 44:281–284, doi:10.​1136/​jmg.​2006.​046425 CrossRefPubMed
21.
Hanein S, Durr A, Ribai P, Forlani S, Leutenegger AL, Nelson I, Babron MC, Elleuch N, Depienne C, Charon C, Brice A, Stevanin G (2007) A novel locus for autosomal dominant “uncomplicated” hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3. Hum Genet 122:261–273, doi:10.​1007/​s00439-007-0396-1 CrossRefPubMed
22.
Metadata
Title
Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia
Authors
Rebecca Schüle
Elisabeth Brandt
Kathrin N. Karle
Maria Tsaousidou
Stephan Klebe
Sven Klimpe
Michaela Auer-Grumbach
Andrew H. Crosby
Christian A. Hübner
Ludger Schöls
Thomas Deufel
Christian Beetz
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Neurogenetics / Issue 2/2009
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-008-0158-9

Other articles of this Issue 2/2009

neurogenetics 2/2009 Go to the issue

Short Communication

Humoral immunodeficiency in congenital insensitivity to pain with anhidrosis

Letter to the Editors

Reply to the “Letter to the Editors” by Steven Buyske

Short Communication

LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity

Original Article

New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP)

Original Article

Gene expression in blood of subjects with Duchenne muscular dystrophy

Original Article

Chromosomal microarray mapping suggests a role for BSX and Neurogranin in neurocognitive and behavioral defects in the 11q terminal deletion disorder (Jacobsen syndrome)