Role of TGDS in Catel-Manzke syndrome

Catel-Manzke syndrome (CMS) is a very rare genetic disease. One very frequent symptom is the Pierre-Robin sequence: the patients present a very small mandibula, cleft palate and the tendency of the tongue to block the airways and the upper digestive tract.  This causes problems for the patients, who can experience difficulties in breathing and eating. The presence of an extra phalanx in the index finger is common. Other alterations are detected in heart, joints and other regions of the skeleton. In some patients a growth delay is observed. The only available therapy is surgery, aimed to ensure airway patency and to eliminate cleft palate, to facilitate breathing and feeding, and to correct the heart defects. Some patients require artificial feeding by a nasogastric tube during the first months/years of life.

The gene affected is TGDS, located on chromosome 13; TGDS function in vertebrates is currently unknown. However, the clinical presentation of CMS is reminiscent of other genetic diseases caused by defects in proteoglycans. Proteoglycans are complex molecules, formed by very long sugar chains linked to a protein backbone; they have many functions and are in particular important for a correct bone, cartilage and organ development.

The project aims to identify the molecular function of TGDS and its involvement in CMS. The results will increase our knowledge about the mechanisms involved in the correct embryonal and fetal development and they will also lead to a better understanding of other genetic diseases affecting skeletal development, posing the basis for possible therapeutic interventions.