neurogenetics

, 10:97

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

  • 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
Original Article

DOI: 10.1007/s10048-008-0158-9

Cite this article as:
Schüle, R., Brandt, E., Karle, K.N. et al. Neurogenetics (2009) 10: 97. doi:10.1007/s10048-008-0158-9

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.

Keywords

CYP7B1Hereditary spastic paraplegiaPolymorphismSPG5

Supplementary material

10048_2008_158_MOESM1_ESM.doc (35 kb)
Supplementary Table 1Previous genetic screens on primary cohort patients (DOC 35.0 KB)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Rebecca Schüle
    • 1
  • Elisabeth Brandt
    • 2
  • Kathrin N. Karle
    • 1
  • Maria Tsaousidou
    • 3
  • Stephan Klebe
    • 4
  • Sven Klimpe
    • 5
  • Michaela Auer-Grumbach
    • 6
  • Andrew H. Crosby
    • 3
  • Christian A. Hübner
    • 2
  • Ludger Schöls
    • 1
  • Thomas Deufel
    • 2
  • Christian Beetz
    • 2
  1. 1.Sektion Klinische NeurogenetikHertie Institut für Klinische HirnforschungTübingenGermany
  2. 2.Institut für Klinische Chemie und LaboratoriumsdiagnostikUniversitätsklinikum JenaJenaGermany
  3. 3.Department of Medical GeneticsSt George’s UniversityLondonUK
  4. 4.Klinik für NeurologieUniversitätsklinikum Schleswig-HolsteinKielGermany
  5. 5.Neurologische KlinikJohannes-Gutenberg-Universität MainzMainzGermany
  6. 6.Institut für Humangenetik und Zentrum für Medizinische ForschungMedizinische UniversitätGrazAustria