Exome sequencing as potential diagnostic tool in Charcot-Marie-Tooth

Exome sequencing has proved itself as a valuable tools for rapid molecular diagnosis, particularly when a disease can be caused by several mutations in different genes. Here is a good example of applying WES to discover new mutations in CMT patients with no mutations in the main disease associated loci.

Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth disease

Byung-Ok Choi, Soo Kyung Koo, Mi-Hyun Park, Hwanseok Rhee, Song-Ju Yang, Kyoung-Gyu Choi, Sung-Chul Jung, Han Su Kim, Young Se Hyun, Khriezhanuo Nakhro, Hye Jin Lee, Hae-Mi Woo, Ki Wha Chung.

Abstract

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is a genetically and clinically heterogeneous disorder with variable inheritance modes. Since several molecules have been reported to have therapeutic effects on CMT, depending on the underlying genetic causes, exact genetic diagnostics have become very important for executing personalized therapy. Whole-exome sequencing has recently been introduced as an available method to identify rare or novel genetic defects from genetic disorders. Particularly, CMT is a model disease to apply exome sequencing, since more than 50 genes (loci) are involved in its development with weak genotype-phenotype correlation. This study performed the exome sequencing in twenty five unrelated CMT patients who revealed neither 17p12 duplication/deletion nor several major CMT genes. This study identified eight causative heterozygous mutations (32%). This detection rate seems rather high, since each sample was tested before the study for major genetic causes. Therefore, this study suggests that the exome sequencing can be a highly exact, rapid, and economical molecular diagnostic tool for CMT patients who are tested for major genetic causes.