Gene/phenotype/disorder under study
MEK2 (MAP2K2), MIM: 601263
BRAF, MIM: 164757
KRAS, MIM: 190070
MAP2K1 (MEK1), MIM: 176872
YWHAZ
Abstract
MEK2 (MAP2K2, MIM: 601263) encodes mitogen activated protein kinase 2, a dual specificity kinase functioning as a core component of the RAS MAPK cascade. This pathway regulates cell proliferation, differentiation, survival, and embryonic development. Pathogenic activation of this signaling axis alters downstream ERK activity, leading to disrupted tissue patterning and impaired homeostatic control. Germline gain of function variants in MEK2 are a known cause of RASopathies, most commonly cardiofaciocutaneous syndrome, and are associated with characteristic craniofacial features, congenital heart defects, ectodermal anomalies, growth impairment, developmental delay, and variable neurologic involvement. Despite MEK2 being an established RAS MAPK component, the phenotypic range attributable to MEK2 variants remains incompletely defined and genotype phenotype correlations are still limited.
We are conducting a comprehensive characterization of individuals carrying pathogenic/likely pathogenic or unkown significance MEK2 variants, aiming to refine the clinical spectrum associated with MEK2 related disorders and to improve understanding of their molecular underpinnings. By assembling an international cohort, we seek collaborators who can contribute additional cases to deepen insight into MEK2 driven dysregulation of RAS MAPK signaling and to advance delineation of the mechanisms shaping the resulting developmental phenotype.
At the same time, we are exploring other mutations that cause CFC syndrome to investigate genotype–phenotype correlations and assess the range of severity scores among affected individuals.
Coordinating clinicians
Dr. K. Śledzińska – ksledzinska@gumed.edu.pl
Prof. J. Wierzba – kwierz@gumed.edu.pl
Institution
Medical Universty of Gdansk, University Clinical Centre, Gdansk, Poland
MEK2 Research Foundation
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