Journal of Neurology

, Volume 259, Issue 8, pp 1673–1685 | Cite as

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

  • G. L. Davidson
  • S. M. Murphy
  • J. M. Polke
  • M. Laura
  • M. A. M. Salih
  • F. Muntoni
  • J. Blake
  • S. Brandner
  • N. Davies
  • R. Horvath
  • S. Price
  • M. Donaghy
  • M. Roberts
  • N. Foulds
  • G. Ramdharry
  • D. Soler
  • M. P. Lunn
  • H. Manji
  • M. B. Davis
  • H. Houlden
  • M. M. Reilly
Original Communication

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 neuropathies Genetics 

Supplementary material

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

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • G. L. Davidson
    • 1
    • 2
  • S. M. Murphy
    • 2
  • J. M. Polke
    • 1
    • 2
  • M. Laura
    • 2
  • M. A. M. Salih
    • 3
  • F. Muntoni
    • 4
  • J. Blake
    • 5
    • 6
  • S. Brandner
    • 7
  • N. Davies
    • 8
  • R. Horvath
    • 9
  • S. Price
    • 10
  • M. Donaghy
    • 11
  • M. Roberts
    • 12
  • N. Foulds
    • 13
  • G. Ramdharry
    • 2
  • D. Soler
    • 14
  • M. P. Lunn
    • 2
  • H. Manji
    • 2
  • M. B. Davis
    • 1
    • 2
  • H. Houlden
    • 1
    • 2
  • M. M. Reilly
    • 2
  1. 1.Neurogenetics UnitNational Hospital for Neurology and NeurosurgeryLondonUK
  2. 2.MRC Centre for Neuromuscular Diseases and Department of Molecular NeuroscienceUCL Institute of Neurology and National Hospital for Neurology and NeurosurgeryLondonUK
  3. 3.Division of Pediatric Neurology, Department of Pediatrics, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
  4. 4.The Dubowitz Neuromuscular CentreUCL Institute of Child HealthLondonUK
  5. 5.Department of Clinical NeurophysiologyNational Hospital for Neurology and NeurosurgeryLondonUK
  6. 6.Department of Clinical NeurophysiologyNorfolk and Norwich University HospitalNorwichUK
  7. 7.Division of Neuropathology, Department of Neurodegenerative DiseaseInstitute of NeurologyLondonUK
  8. 8.Department of NeurologyQueen Elizabeth HospitalBirminghamUK
  9. 9.Institute of Genetic MedicineNewcastle UniversityNewcastle upon TyneUK
  10. 10.Department of Clinical GeneticsOxford Radcliffe HospitalOxfordUK
  11. 11.Department of Clinical NeurologyUniversity of Oxford, John Radcliffe HospitalOxfordUK
  12. 12.Department of NeurologyUniversity Hospital of South ManchesterManchesterUK
  13. 13.Clinical Genetics ServiceSouthampton University Hospitals TrustSouthamptonUK
  14. 14.Department of PaediatricsMater Dei HospitalMsidaMalta

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