Manole, A;
Chelban, V;
Haridy, NA;
Hamed, SA;
Berardo, A;
Reilly, MM;
Houlden, H;
(2016)
Severe axonal neuropathy is a late manifestation of SPG11.
Journal of Neurology
, 263
(11)
pp. 2278-2286.
10.1007/s00415-016-8254-5.
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Abstract
Complex hereditary spastic paraplegia (HSP) is a clinically heterogeneous group of disorders usually inherited in an autosomal recessive manner. In the past, complex recessive spastic paraplegias have been frequently associated with SPG11 mutations but also with defects in SPG15, SPG7 and a handful of other rare genes. Pleiotropy exists in HSP genes, exemplified in the recent association of SPG11 mutations with CMT2. In this study, we performed whole exome sequence analysis and identified two siblings with novel compound heterozygous frameshift SPG11 mutations. The mutations segregated with disease were not present in control databases and analysis of skin fibroblast derived mRNA indicated that the SPG11 truncated mRNA species were not degraded significantly by non-sense mediated mRNA decay. These siblings had severe early-onset spastic paraplegia but later in their disease developed severe axonal neuropathy, neuropathic pain and blue/black foot discolouration likely caused by a combination of the severe neuropathy with autonomic dysfunction and peripheral oedema. We also identified a similar late-onset axonal neuropathy in a Cypriot SPG11 family. Although neuropathy is occasionally present in SPG11, in our SPG11 patients reported here it was particularly severe, highlighting the association of axonal neuropathy with SPG11 and the late manifestation of axonal peripheral nerve damage.
| Type: | Article |
|---|---|
| Title: | Severe axonal neuropathy is a late manifestation of SPG11 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00415-016-8254-5 |
| Publisher version: | http://dx.doi.org/10.1007/s00415-016-8254-5 |
| Language: | English |
| Additional information: | © The Author(s) 2016 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, Axonal neuropathy, Spatacsin, CMT2, Gene, Genetics, SPG11, HEREDITARY SPASTIC PARAPLEGIA, THIN CORPUS-CALLOSUM, MUTATIONS, GENE, HETEROGENEITY, DEGENERATION, DOMINANT |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1517075 |
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