Genetics of the Ehlers-Danlos syndrome: more than collagen disorders

作者：Van Damme Tim; Syx Delfien; Coucke Paul; Symoens Sofie; De Paepe Anne; Malfait Fransiska^*

来源：Expert Opinion on Orphan Drugs, 2015, 3(4): 379-392.

DOI：10.1517/21678707.2015.1022528

• clinical features
• collagen
• connective tissue
• Ehlers-Danlos syndrome
• genotype
• glycosaminoglycan
• mutation
• next-generation sequencing
• phenotype

Introduction: The Ehlers-Danlos syndrome (EDS) comprises a clinically and genetically diverse group of heritable connective tissue disorders, characterized by joint hypermobility, skin hyperextensibility and generalized connective tissue friability. Although the initially characterized subtypes were shown to result from defects in fibrillar collagens (types I, III, V) or their modifying enzymes, recent discoveries have implicated other molecules, such as tenascin X and glycosaminoglycan synthesis enzymes, in the pathogenesis of these disorders.
Areas covered: This article summarizes the current knowledge on the biosynthesis of collagen fibrils and focuses on the molecules involved in this process, especially those relevant to the pathogenesis of EDS. It also provides an overview of the general clinical presentation of EDS and the genetic defects underlying its different subtypes.
Expert opinion: The recent identification of several novel types of EDS has greatly expanded its clinical and genetic heterogeneity, and the genomic era promises to provide even more insights into the molecular basis of unresolved types of EDS. At the same time the underlying pathophysiologic mechanisms in these disorders are still poorly understood. Therefore, future research should focus on the elucidation of these mechanisms, and the identification of clinically reliable biomarkers and targetable signaling pathways and cellular processes.

• 出版日期2015-4