Research for Rare - Research for rare diseases


RASopathies constitute a heterogeneous group of disorders with a common molecular pathogenesis and overlapping phenotypic patterns. Noonan, cardiofaciocutaneous, Costello, and LEOPARD syndromes belong to this group, as well as neurofibromatosis type 1 and Legius syndrome. Dysregulation of RAS-dependent signaling due to a germline mutation in one of the pathway components cause a variety of developmental abnormalities such as heart defects, short stature, facial anomalies, cognitive impairment and others. Interestingly, based on the known molecular basis and supported by preliminary animal studies, RASopathies are considered as disorders that might be amenable to treatment with small molecules. However, translation into clinical trials is still hampered by a limited understanding about the precise mechanisms on cellular and organ levels. There is also a lack of valid genotype-phenotype and long-term follow-up data, making it difficult to define therapeutic targets. This consortium aims to fill some of these gaps by a multidisciplinary and multimodal approach. GeNeRare aims to address in particular the pathophysiology and molecular pathogenesis of organ involvement that is critical for long-term outcome, namely development of hypertrophic cardiomyopathy and neurocognitive impairments. But the consortium will also study novel aspects such as epidermal differentiation and cellular senescence. Collection of valid genotype phenotype data as well as the investigation of neurophysiologic parameters in affected humans define further lines of translation of basic research to patient care.

University Hospital Magdeburg
Institute of Human Genetics
Leipziger Str. 44
39120 Magdeburg
Tel.: +49-(0)391-67-15062
Fax: +49-(0)391-67-15066