Molecular basis of hereditary connective tissue disorders

Heritable connective tissue disorders (HCTDs) are a large group of genetically determined syndromes, which involve several organs and systems consisting mainly of connective tissue, particularly the cutaneous, cardiovascular, articular, ocular, and bone systems. Mutations in genes, which encode for structural proteins, proteoglycans, and enzymes and growth factors that regulate their maturation and synthesis, are responsible for some hundreds of specific disorders. These diseases are mainly transmitted in an autosomal dominant manner, but also autosomal recessive transmission is present in cases where genes encoding enzymes and/or transcription/growth factors are affected, or for proteins with a regulatory and non-structural effect. Given the rarity of these genetic diseases, there are few specialists currently dealing with their clinical and molecular definition both in Italy and abroad. Research goals: - Develop knowledge on hereditary connective tissue diseases with prevalent cutaneous, musculoskeletal and vascular involvement, both from a clinical and molecular point of view. - Define specific clinical and molecular approaches for the diagnosis of rare and ultra-rare hereditary connective tissue diseases. - Define the genetic basis of hypermobile Ehlers-Danlos syndrome and related phenotypes. - Define updated and effective guidelines for early diagnosis and for an adequate multidisciplinary support for patients with hereditary connective disorders. - Set up the Italian registry of patients suffering from Ehlers-Danlos syndromes in collaboration with Italian diagnostic centers and specialists. - Promote the dissemination of knowledge on hereditary connective disorders, at local, national and international level between specialists, patient associations and patients.