High prevalence of rare ryanodine receptor type 1 variants in patients suffering from aneurysmatic subarachnoid hemorrhage: A pilot study
| Autor: | Thomas Kapapa, Karin Jurkat-Rott, Jan Coburger, Cristian Rainer Wirtz, Werner Klingler |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Subarachnoid hemorrhage Population 030232 urology & nephrology Pilot Projects Disease Aneurysm Ruptured Gastroenterology 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Prevalence medicine Humans cardiovascular diseases education RYR1 education.field_of_study business.industry Abnormal bleeding Malignant hyperthermia Intracranial Aneurysm Ryanodine Receptor Calcium Release Channel Vasospasm General Medicine Subarachnoid Hemorrhage musculoskeletal system medicine.disease nervous system diseases Phenotype Neurology Hemostasis Mutation Female Surgery Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Neuroscience. 45:209-213 |
| ISSN: | 0967-5868 7393-3023 |
| Popis: | Subarachnoid hemorrhage (SAH) remains a challenging neurosurgical disease. The ryanodine receptor type 1 Ca2+ channel (RyR1) plays a crucial role in vasoconstriction and hemostasis. Mutations of the encoding gene, RYR1, are known to cause susceptibility to malignant hyperthermia (MH). Recently, a RYR1 mutation was found to be associated with abnormal bleeding times. Therefore, an assessment of the RYR1 gene might be of high relevance in patients with aneurysmatic SAH. In the presented pilot study, we screened 10 patients suffering from SAH for RYR1 variants and, for the first time in SAH, performed an assessment of pathogenicity of these variants using protein prediction software. Four of the patients showed a RYR1 variant. For three of the variants, p.Glu79Lys, p.Arg885C, p.Glu2635 Val, all three programs predicted pathogenicity. Their prevalence in the general population is very low i.e. under 0.005%. For the fourth variant, p.Pro4501Leu (RS73933023), the results of the prediction programs were discrepant and the prevalence in the general population was high, i.e. almost 0.5%, which is too frequent to be associated with the rare SAH phenotype. Clinical evaluation revealed that no differences concerning neurological outcome, presence of vasospasm, ischemic deficits and mean hospital stay between patients with and without variants were found. However, in our series SAH patients have an increased frequency of rare RYR1 variants. Hence, potentially contributing to the pathogenesis of SAH. Further data is needed to confirm this preliminary result. |
| Databáze: | OpenAIRE |
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