Peer-review started: August 15, 2014
First decision: October 17, 2014
Revised: November 14, 2014
Accepted: November 27, 2014
Article in press: December 31, 2014
Published online: February 2, 2015
Processing time: 158 Days and 19.7 Hours
During the past few decades, the investigative tech-nologies of molecular biology - especially sequencing - underwent huge advances, leading to the sequencing of the entire human genome, as well as the identification of several candidate genes and the causative genetic variations that are responsible for monogenic skin diseases. These advances provided a solid basis for subsequent studies elucidating mechanisms of monogenic skin diseases and improving our understanding of common skin diseases. Furthermore, these discoveries also contributed to the development of novel therapeutic modalities for monogenic skin diseases. In this review, we have used the disease spectrum caused by mutations in the CYLD gene - Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma type 1 - as a model for demonstrating the knowledge explosion for this group of diseases.
Core tip: Although dermatology is a morphology-orientated specialty, genetic investigation can help understand the events taking place in the skin of the affected patients. Genetic investigation of Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma type 1 further supported the clinical hypothesis that these monogenic skin diseases are not different entities, but rather clinical variants of a disease spectrum caused by mutations in the cylindromatosis (CYLD) gene. In addition to understanding the underlying mechanisms of these allelic variants, genetic investigation can also accelerate the development of novel therapeutic modalities, such as therapy using tropomyosin-receptor-kinase specific lestaurtinib for patients with germline CYLD mutations.