Jones, Victoria Jane;
(2020)
Spinal Lipoma: Developing a Biomarker and Developmental Mechanisms.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Victoria Jones Thesis Edited Version.1.pdf Download (18MB) | Preview |
Abstract
Lumbosacral lipomas (LSL) are a common form of closed spinal dysraphism occurring in 1 in 4000 live births. There is no established theory to explain origin, no animal models and no genetic or environmental association. In addition to the uncertainty that underlies the pathogenesis there are also unanswered clinical questions, with the timing of surgical intervention a difficult balance between prevention of neurological deterioration and avoidance of unnecessary surgery. Wykes et al. have demonstrated that not all children go onto develop symptoms in the first 10 years of life and therefore timing of surgery becomes an important issue. This thesis attempts to answer two questions – is there a biomarker that can be used to guide timing of surgery, and what is the underlying pathogenesis of LSL? Samples of cerebrospinal fluid (CSF), blood and urine were collected from patients undergoing near total resection of LSL. High performance liquid chromatography/mass spectrometry (HPLC/MS) was used to determine the lipid profile of samples and a scoring system developed to correlate lipid results with severity of symptoms. In addition, Whole Genome Sequencing was performed on two families with familial cases of LSL and analysed in combination with Whole Exome Sequencing from two further individuals with LSL. HPLC/MS confirmed a significant difference in phospholipids and targeted assay revealed lysophosphatidylcholine 18:2 and phosphatidylcholine 36:2 to be significantly different in CSF and blood samples respectively. These results not only have potential for development of a biomarker to guide clinical management but also hint at an underlying mechanism of neurological deterioration due to bioavailability of docosahexaenoic acid in CSF. Genetic analysis identified a number of different variants in LSL patients highlighting the complexity of pathogenesis. Identification of stop gain variants in ADAMTS20 and NDTS1 supports earlier work relating LSL pathogenesis to failure in neural crest differentiation and migration.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Spinal Lipoma: Developing a Biomarker and Developmental Mechanisms |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices 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 Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10115697 |
Archive Staff Only
 |
View Item |
