TP1

TP1

Gene mutations and clinical expression in Noonan syndrome and related disorders: consequences for diagnostics and management

This subproject is focused on clinical genetic and translational aspects of RASopathies. Research activities are directed towards diagnostics, 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 development of innovative molecular genetic diagnostics based on high-throughput sequencing, the exploration of correlations between specific genetic changes and disease course and prognosis, as well as the establishment of specialized structures for patient care as a national reference center for RASopathies. 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 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 updated and equipped with novel software tools to facilitate the analysis of mutation spectrum and genotype phenotype correlations on a broad basis of standardized data. 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: Fachzentrum für RASopathien).

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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. Development and validation of innovative molecular genetic diagnostics based on high-throughput sequencing.
  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. Establishment of a national patient registry.
  4. Further development of an interdisciplinary RASopathy clinics at the University Hospital Magdeburg will be further expanded and integrated into a national reference center for RASopathies.

Publications:



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