In CMT, there is a large variation in disease onset, severity, or progression, often seen among individuals with the same genetic subtype of a disease, even within a single family.  Genetic modifiers play important roles in such variations, known as heterogeneity.

Modifier genes can interact both directly and indirectly with the primary disease-causing gene to exacerbate or reduce the characteristics of the disease. Modifier genes can also give insights into disease mechanisms, predict the course of disease, or even serve as therapeutic targets.

Identification and study of modifier genes is an active area of research in CMT.  For example, it’s been documented that variants in the LITAF gene contribute to a more severe and earlier onset form of CMT1A, whereas variants in JPH1 lead to more severe symptoms in CMT2K.  New modifier gene candidates for patients with CMTA1A were identified earlier this year but further work is required to understand the role of these genes.

Genetic modifiers are an exciting area of research that CMTRF will continue to monitor and work with scientists to harness their potential therapeutic benefit.

by Grace Pavlath, PhD, Chief Science Officer