Advances in genetic research and diagnosis of Charcot-Marie-Tooth disease

Abstract

　Charcot-Marie-Tooth disease ( CMT ) is a type of inherited peripheral neuropathy ( IPN ) that primarily affects motor and sensory nerves due to abnormalities in the peripheral nervous system. CMT exhibit significant genetic and clinical heterogeneity, with over 140 causative genes identified, encompassing diverse cellular localizations and functional roles. This review discusses advancements in genetic analysis techniques, including gene panel sequencing, whole-exome sequencing ( WES ) , whole-genome sequencing ( WGS ) , and long-read sequencing, which have significantly improved the diagnostic accuracy and yield. Furthermore, we also present the genetic landscape of 3,315 CMT/IPN patients in Japan ( excluding PMP22 duplication/deletion cases ) . Comprehensive analyses are essential to deepen our understanding of CMT/IPN and facilitate the development of targeted therapies and improved patient care. The discovery of repeat expansion mutations emphasizes the necessity for continuous refinements in diagnostic strategies to address novel and emerging genetic mechanisms underlying CMT/IPN.