Targeted genes/syndromes under study:
o Noonan syndrome: OMIM #PS163950
o Noonan syndrome-like disorder with loose anagen hair: OMIM #PS607721
o Noonan syndrome with multiple lentigines (LEOPARD syndrome): OMIM #PS151100
o Noonan syndrome-like disorder with or without JMML: OMIM #613563
o CFC syndrome: OMIM #PS115150
o Costello syndrome: OMIM #218040
Abstract
Recently, an increasing number of case reports have suggested a higher incidence of autoimmune diseases and immune dysregulation in patients with RASopathy. Pathogenic variants in SHOC2 but possibly also in other RASopathy genes appear to increase the susceptibility to the development of autoimmune diseases. On the molecular level, the emerging understanding of the role of the RAS-MAPK pathway in cells of the immune system provides the first clues to potential mechanisms of immune dysregulation. However, robust evidence linking RASopathies to autoimmune diseases is still lacking, and the full spectrum of associated diseases, possible genotype-phenotype correlations, and potential biomarkers remain unknown.
To address current knowledge gaps, this study will retrospectively collect and statistically analyze clinical, genetic, and immunological data from patients with RASopathies who have
experienced autoimmune or autoinflammatory diseases. Data collection will be performed using an Excel-based questionnaire. By including all patients with a molecular diagnosis of a RASopathy and any type or severity of autoimmune/autoinflammatory disorder, the study aims to provide new insights into the (auto)immune phenotype of RASopathies, potentially guiding future research on molecular mechanisms and informing clinical management strategies.
Coordinating clinicians
Darius Amirmoini, M.D. student – darius.amirmoini@st.ovgu.de
Prof. Dr. med. Martin Zenker
Institution
Institute of Human Genetics, University Hospital Magdeburg, Germany
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: No
3- Linked to a translational/basic research project: No