Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gesselbauer, J.
Phänotypisches Spektrum Kollagen 1-assoziierter Bindegewebserkrankungen
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 76
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Geigl Jochen Bernd
- Verheyen Sarah
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- Abstract:
- The main objective of this thesis is to write a clinical report about a patient carrying a mutation in COL1A1, one of the two genes encoding collagen I, an extracellular matrix protein. Mutations in COL1A1 and COL1A2 have been known to cause different hereditary connective tissue disorders with a broad spectrum of phenotypes, most importantly Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS). However, not all patients may be easily categorized due to inconclusive presentation of symptoms. In recent years a new entity, i.e., combined Osteogenesis imperfecta and Ehlers-Danlos syndrome 1 and 2 (COL1-related overlap disorder, C1ROD), has been evolved, which further illustrates the complexity in diagnosing these diseases. In this work, a systematic review of the literature, regarding COL1-related hereditary connective tissue disorders is conducted in PubMed. The clinical symptoms of our patient will be compared with the existing clinical descriptions and preexisting categories of COL1-related diseases. The case report of our patient will be further adapted and submitted for publication. Methods The review of the literature was performed in PubMed. The clinical presentation is based on medical history, radiographs, clinical descriptions, and genetic results of a 33-year-old patient with symptoms of both of OI and EDS. The genetic results include data from Whole-Exome sequencing which were performed after informed consent was obtained. Results A clear clinical diagnosis based on the patient’s phenotype, i.e., short stature, joint hypermobility, several subluxations, and distinct facial features, could not be made. Whole-Exome sequencing was performed, a yet unknown variant in COL1A1 (NM_000088.3: c.2885G>T) was detected. The variant was not found in the parents’ blood samples and was therefore assumed to be de-novo. As most of the symptoms of the patient are consistent with both OI and EDS a diagnosis of C1ROD was made retrospectively. Conclusion There have been many attempts to define COL1-related diseases as independent entities, however, this has proven to be difficult. Case reports, as the one presented in this thesis, show the broad spectrum of phenotypes associated with variants in COL1A and underline the purpose of the introduction of the new defined entity C1ROD. In addition, it emphasizes the importance of genetic testing as some phenotypes are not consistent with the classic clinical descriptions of established entities available in the literature.