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Mutation in FAM134B causing severe hereditary sensory neuropathy
  1. Sinéad M Murphy1,
  2. Gabrielle L Davidson1,
  3. Sebastian Brandner2,
  4. Henry Houlden1,
  5. Mary M Reilly1
  1. 1MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK
  2. 2Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
  1. Correspondence to S M Murphy, MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, 8–11 Queen Square, London WC1N 3BG, UK; sinead.murphy{at}uclh.nhs.uk

https://doi.org/10.1136/jnnp.2010.228965

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    The hereditary sensory and autonomic neuropathies (HSAN) are rare inherited neuropathies presenting with sensory loss and complications, including ulcers, infections, osteomyelitis and amputations. Usually, sensory symptoms predominate although motor involvement can occur. Autonomic features may be minimal (then hereditary sensory neuropathy, HSN, is preferred). HSAN has been classified into five subtypes depending on clinical presentation.1

    Hereditary sensory and autonomic neuropathy II (HSANII or HSNII) is an early onset, autosomal recessive sensory neuropathy with ulcero-mutilating complications due to mutations in the HSN2 isoform of the WNK1 gene.2 Recently, a similar phenotype was described in a Saudi-Arabian family, and a homozygous nonsense mutation found in a new gene, FAM134B (family with sequence similarity 134, member B), encoding a newly identified Golgi protein. The index case in this family was initially thought to have leprosy. Three additional families (out of 75 patients) with similar phenotypes were found to have homozygous loss of function mutations in FAM134B.3

    Here, we report the clinical and pathological findings in a further patient with HSNII due to a homozygous mutation in FAM134B.

    Case report

    The patient (III-2) is from a consanguineous Somalian family (figure 1A) and had a normal birth and developmental milestones. She had recurrent foot infections and ulcers from the age of 5 years, and a right forefoot amputation aged 10 years. She started using a wheelchair aged 11 years. She described feeling pain and sweating normally. A cousin (III-7) had similar symptoms of recurrent infections and amputations.

    Figure 1

    (A) Filled symbols=affected; empty symbols=unaffected; cross-slashed symbols=deceased; double line=consanguinity. The proband is indicated by the arrow. (B) Radiographs of the hands and ankles. (C–E) Sural …

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    Footnotes

    • Funding MMR has received funding/grant support from the Medical Research Council (MRC) and the Muscular Dystrophy Campaign. HH has received funding/grant support from the NIHR UCLH/UCL Comprehensive Biomedical Research Centre (CBRC), the MRC (MRC Centre and HH fellowship, G108/638 and G0802760) and the Muscular Dystrophy Association (MDA). This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme.

    • Competing interests None.

    • Ethics approval This study was conducted with the approval of the Joint Medical and Ethics Committee at The National Hospital for Neurology and Neurosurgery.

    • Provenance and peer review Not commissioned; externally peer reviewed.