TP1

Mutation spectrum, genotype phenotype correlations, natural history and clinical management of RASopathies

This subproject is focused on clinical genetic and translational aspects of RASopathies. Research activities are directed towards clinical classification, genotype phenotype correlations, and improvement of patient care for RASopathies.  Directed by Martin Zenker, a pediatrician and clinical genetic scientist with long-standing expertise in RASopathies, this subproject aims at the further development of a comprehensive database for gene variations and standardized phenotype data, the exploration of correlations between specific genetic changes and disease course and prognosis, as well as the further development of specialized structures to improve patient care. The subproject also provides an important platform for translational approaches through its direct connection to patients and support groups.

TP1-Picture-1
Legend: The RAS-MAPK pathway and associated human diseases caused by gain-of-fucntion germline mutations in its respective components.

The existing online mutation database (www.nseuronet.com), which was developed in 2010 as a mutation and genotype-phenotype database for RASopathies in the context of a previous ERA-Net for Research Programmes on Rare Diseases, will be continuously updated and equipped with novel software tools. A national patient registry will be developed and an interdisciplinary RASopathy clinics at the University Hospital Magdeburg will be further expanded and integrated into a national reference center for RASopathies under the umbrella of the “Mitteldeutsches Kompetenznetz für Seltene Erkrankungen” (MKSE: www.mkse.ovgu.de/Fachzentren).

TP1-Picture-2
Legend: The NSEuroNet database is an updated online source for mutations in RASopathy genes and associated phenotypic features.

We are closely collaborating with family support groups:
Noonan-Kinder e.V.
CFC Angels e.V.

Major goals:

  1. Further development of the NSEuroNet database (www.nseuronet.com) as a comprehensive resource for the classification of variations in RASopathy genes
  2. Collection of standardized clinical and genetic data in order to explore genotype-phenotype correlations and natural history in large cohorts with defined subtypes of RASopathies
  3. Identification and characterization of novel genes and genetic mechanisms for RASopathies
  4. Establishment of a national patient registry
  5. Generation and further development of information materials on RASopathies for affected individuals and their families
  6. Collection of biomaterials from affected individuals for research goals fo the consortium
  7. Operation of genomic and transcriptomic analyses in collaboration with consortium partners

Publications:



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