About Epistem: Ectodermal dysplasia syndromes (EDS)
EEC syndrome is one of a family of human syndromes that share one or more of three cardinal features. ADULT: acro-dermato-ungual-lacrimal-tooth syndrome, AEC: Hay Wells syndrome, LMS: Limb-mammary syndrome, RHS: Rapp-Hodgkin syndrome, EEC: Ectrodactyly, Ectodermal dysplasia and Cleft lip/palate syndrome, LADD: Lacrimo-Auriculo-Dento-Digital Syndrome, ECP: Ectrodactyly-cleft palate syndrome. [fig.: Dr. H. van Bokhoven]
The ectodermal dysplasia syndromes (EDS) are a group of inherited autosomal dominant human diseases. The disorders are congenital, diffuse, and nonprogressive. Morbidity and mortality is related to the absence or presence of eccrine and mucous glands. Children with decreased sweating may have a mortality rate of up to 30% in infancy or early childhood. Recurrent high fever may lead to seizures and neurological pathology. Collectively, the prevalence of EDS is estimated at 7 cases in 10,000 births. There is no specific treatment for these disorders. The prototypic Ectrodactyly, Ectodermal dysplasia and Cleft lip/palate (EEC) syndrome (OMIM 604292) has highly variable expressivity and reduced penetrance. It is clinically characterized by ectodermal dysplasia affecting skin, hair, nails and teeth, and facial clefts. In addition, EEC patients show lachrymal duct abnormalities, urogenital problems, hearing loss, facial dysmorphism, respiratory infections and developmental retardation. Several congenital diseases have been described that share features with or resemble the EEC in few of its cardinal features. These diseases have been linked to mutations in the gene coding for the p63* protein, the main study object in this project. Mice devoid of both copies of the p63 gene were born lacking limbs as well as skin and appendages, such as hair shafts, follicles and sebaceous glands. p63-deficient mice also lack tooth primordia, mammary tissues, prostate, bladder, eyelids and a wide range of other tissues. All of these defects have been observed in patients carrying heterozygous (dominant) p63 mutations. Thus, It is of major importance to understand the role of p63 in EDS to develop new strategies for treatment of these rare diseases.
The increasing impact on society and medicine of the exploration of the human genome resources has been governed by an increased worldwide effort of basic, clinical and pharmaceutical science to understand and to correct the molecular basis of genetic disorders. EDS diseases are a striking example of rare diseases for which no current therapeutic approaches available. These considerations make it mandatory to significantly widen our knowledge on the genetic and molecular mechanisms of disease and integrate the interconnections of each. This necessitates basic and translational research covering a wide range of aspects that cannot be handled by single research entities. The need for an interdisciplinary, integrative effort at a European level is apparent, and the expertise of the different participants will form a comprehensive, cooperative project. The groups involved in the Epistem project provide a very high knowledge in the field. They also provide proprietary concepts that allow the generation of new biological reagents with high therapeutic potential and they will provide appropriate cellular and animals models of disease combined with a profound knowledge of the molecular and cellular biology and pathophysiology of these disease models.
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