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


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.

DOI: 10.1007/s00415-011-6397-y

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@article{Davidson2011FrequencyOM, title={Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort}, author={Gabrielle L Davidson and S Murphy and James M. Polke and Matilde Laur{\'a} and Mustafa A Salih and Francesco Muntoni and Julian C. Blake and Sybille Brandner and Nada Davies and Rita Horvath and Sue M. Price and Michael J Donaghy and MJD Roberts and Nicola C. Foulds and Gita M Ramdharry and Dayana Soler and M. P. Lunn and Hadi Manji and Mary Beth Davis and Henry Houlden and Mary M Reilly}, journal={Journal of Neurology}, year={2011}, volume={259}, pages={1673-1685} }