Warburg-Cinotti syndrome (WRCN) and DDR2 gene
Warburg-Cinotti syndrome is a rare, genetic disease affecting external and internal skin tissues. Patients suffering from WRCN develop keloid-like plaques and ulcers, experience progressing flexion contractures, facial and limb deformation, as well as loss of hearing and vision.
Warburg-Cinotti syndrome is caused by missense mutations in DDR2 gene. Healthy DDR2 produces a protein called Discoidin Domain Receptor Tyrosine Kinase 2 (picture above), which is involved collagen-related pathways. Incorrect DDR2 gene leads to disruptions in collagen sensing, improper function of fibroblast cells, and results in disruptions of tissue development.
Xu et al. (2018) identified two mutations contributing to WRCN. Mutation from thymine to cytosine at 1829th position leads to change of amino acid from leucine to proline. Another mutation, from adenosine to guanine at 2219th positions causes change from tyrosine to cysteine.
Discoverer of the syndrome, Mette Warburg, described symptoms in 2006 as:
- vascularized cornea
- retinal dystrophy
- loss of subcutaneous fat over the extremities and the face
- conductive hearing loss
Benign symptoms of Warburg-Cinotti syndrome can manifest itself after birth. During later life, patients develop more severe features.
Scientists reported six patients with Warburg-Cinotti syndrome between 2006 and 2018. Details of research history and individual patients are thoroughly described at OMIM.