Genetics of Connective Tissue Diseases: State of the Art and Perspectives

Resumo

Current problems and some future perspectives of molecular genetic study of connective tissue diseases (CTDs) are reviewed. The corresponding clinical manifestation and mode of heritable disorders of connective tissue (HDCT) inheritance are subdivided into inherited, mostly monogenic, forms and mixed or multifactorial dysplasia of connective tissue (MDCTs). Both forms, especially MDCT, pose significant problems for precise clinical diagnostics. Implementation of modern DNA technologies includes new generation sequencing and clinical exome sequencing which provided a substantial impact in understanding the complex molecular genetic background of CTDs. Owing to new technologies, hundreds of new causative genes of CTDs were found and many commercial gene panels were designed for more precise and objective diagnostics of different CTDs. The results of implementation of NGS for analysis of both HDCTs and especially MDCTs complicated with common syntropic diseases as well as some new data on epigenetic causes of CTDs are briefly summarized. Special attention is paid to biological models and cell culture technologies complemented results of NGS in CTDs. Obvious advantages, relevant problems, and definite limitations in clinical implication of NGS for CTDs studies are discussed.