رسالة جامعية
Explaining disease variability in Pseudoxanthoma elasticum and related disorders
| العنوان: | Explaining disease variability in Pseudoxanthoma elasticum and related disorders |
|---|---|
| المؤلفون: | De Vilder, Eva |
| المساهمون: | Vanakker, Olivier, Leroy, Bart |
| بيانات النشر: | Universiteit Gent. Faculteit Geneeskunde en Gezondheidswetenschappen |
| سنة النشر: | 2021 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences |
| الوصف: | PXE is a rare autosomal recessive ectopic mineralization disease, leading to multi-organ manifestations, including the skin, eyes and cardiovascular system. When taking into account an estimated prevalence of one in 50’000, at least 140’000 individuals are affected worldwide. This number probably is an underestimation, given the disease’s later onset and distinct clinical variability. The observed absence of strong genotype-phenotype correlations in PXE is considered a major limitation for personalized patient care. Hence, a central aim of this dissertation was to contribute to unraveling disease variability in PXE and in this way pave the way for a more personalized approach for PXE patient follow-up. In addition, PXE was used as a starting point to expand what is known about variability of related rare phenotypes and more common, complex diseases. This multi-layered approach emphasizes the relevance of rare disease research and demonstrates how this acquired knowledge can have implications at a larger scale. A first part of this dissertation focused on the identification and validation of modifier genes for the clinical manifestations of PXE. We were able to validate VEGFA as a genetic modifier for the PXE retinopathy and identify NLRP1, SELE, CSF1R and TRPV1 as candidate modifier genes for the cardiovascular phenotype. Additionally, IL1B-related signaling was suggested as a new player in the PXE pathophysiology. Further research is necessary to ascertain the clinical usefulness of these findings for patient follow-up and treatment in patient-centered translational studies. A second part was dedicated to other mechanisms to explain disease variability in PXE and GGCXrelated disorders. Our finding of germline mosaicism as a possible inheritance pattern for PXE and other autosomal recessive genodermatoses can affect patient counseling, especially preconception counseling, as it influences the recurrence risk for future children of affected couples and it is a caveat for implementation of expanded carrier ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/8686618Test; http://hdl.handle.net/1854/LU-8686618Test; https://biblio.ugent.be/publication/8686618/file/8686621Test |
| الإتاحة: | https://biblio.ugent.be/publication/8686618Test http://hdl.handle.net/1854/LU-8686618Test https://biblio.ugent.be/publication/8686618/file/8686621Test |
| حقوق: | No license (in copyright) ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.B3862C86 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |