UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Case Reports
  • Authors:
    Dick KJ, Eckhardt M, Paisán-Ruiz C, Alshehhi AA, Proukakis C, Sibtain NA, Maier H, Sharifi R, Patton MA, Bashir W, Koul R, Raeburn S, Gieselmann V, Houlden H, Crosby AH
  • Publication date:
    04/2010
  • Pagination:
    E1251, E1260
  • Journal:
    Hum Mutat
  • Volume:
    31
  • Issue:
    4
  • Status:
    Published
  • Country:
    United States
  • Language:
    eng
  • Keywords:
    Adolescent, Adult, Animals, Brain, CHO Cells, Child, Child, Preschool, Chromatography, Thin Layer, Consanguinity, Cricetinae, Cricetulus, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Mixed Function Oxygenases, Mutation, Pedigree, Pregnancy, Spastic Paraplegia, Hereditary, Transfection
Abstract
Hereditary spastic paraplegia (HSP) describes a heterogeneous group of inherited neurodegenerative disorders in which the cardinal pathological feature is upper motor neurone degeneration leading to progressive spasticity and weakness of the lower limbs. Using samples from a large Omani family we recently mapped a gene for a novel autosomal recessive form of HSP (SPG35) in which the spastic paraplegia was associated with intellectual disability and seizures. Magnetic resonance imaging of the brain of SPG35 patients showed white matter abnormalities suggestive of a leukodystrophy. Here we report homozygous mutations in the fatty acid 2-hydroxylase gene (FA2H) in the original family used to define the SPG35 locus (p.Arg235Cys) as well as in a previously unreported Pakistani family with a similar phenotype (p.Arg53_Ile58del). Measurement of enzyme activity in vitro revealed significantly reduced enzymatic function of FA2H associated with these mutations. These results demonstrate that mutations in FA2H are associated with SPG35, and that abnormal hydroxylation of myelin galactocerebroside lipid components can lead to a severe progressive phenotype, with a clinical presentation of complicated HSP and radiological features of leukodystrophy. (c) 2010 Wiley-Liss, Inc.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Department of Neuromuscular Diseases
Author
Clinical and Movement Neurosciences
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by