Journal of Neurology

, Volume 259, Issue 8, pp 1673–1685

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort

Authors

  • G. L. Davidson
    • Neurogenetics UnitNational Hospital for Neurology and Neurosurgery
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • S. M. Murphy
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • J. M. Polke
    • Neurogenetics UnitNational Hospital for Neurology and Neurosurgery
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • M. Laura
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • M. A. M. Salih
    • Division of Pediatric Neurology, Department of Pediatrics, College of MedicineKing Saud University
  • F. Muntoni
    • The Dubowitz Neuromuscular CentreUCL Institute of Child Health
  • J. Blake
    • Department of Clinical NeurophysiologyNational Hospital for Neurology and Neurosurgery
    • Department of Clinical NeurophysiologyNorfolk and Norwich University Hospital
  • S. Brandner
    • Division of Neuropathology, Department of Neurodegenerative DiseaseInstitute of Neurology
  • N. Davies
    • Department of NeurologyQueen Elizabeth Hospital
  • R. Horvath
    • Institute of Genetic MedicineNewcastle University
  • S. Price
    • Department of Clinical GeneticsOxford Radcliffe Hospital
  • M. Donaghy
    • Department of Clinical NeurologyUniversity of Oxford, John Radcliffe Hospital
  • M. Roberts
    • Department of NeurologyUniversity Hospital of South Manchester
  • N. Foulds
    • Clinical Genetics ServiceSouthampton University Hospitals Trust
  • G. Ramdharry
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • D. Soler
    • Department of PaediatricsMater Dei Hospital
  • M. P. Lunn
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • H. Manji
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • M. B. Davis
    • Neurogenetics UnitNational Hospital for Neurology and Neurosurgery
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
  • H. Houlden
    • Neurogenetics UnitNational Hospital for Neurology and Neurosurgery
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
    • MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and Neurosurgery
Original Communication

DOI: 10.1007/s00415-011-6397-y

Cite this article as:
Davidson, G.L., Murphy, S.M., Polke, J.M. et al. J Neurol (2012) 259: 1673. doi:10.1007/s00415-011-6397-y

Abstract

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Keywords

Hereditary sensory and autonomic neuropathiesGenetics

Supplementary material

415_2011_6397_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 33 kb)

Copyright information

© Springer-Verlag 2012