Clinical Domain Working Groups

Of the more than 100 genes associated with CMT, the most common and well-known being PMP22, we have chosen three genes for variant curation based on the potential for therapeutic management, MFN2 (Mitofusin 2), GDAP1(ganglioside-induced differentiation-associated protein 1) and SORD (sorbitol dehydrogenase).

Presently, there are several therapeutic developments in process for Mitofusin 2-related CMT. It is by far the most common axonal form of CMT with reasonably high polymorphic allelic heterogeneity, (https://pubmed.ncbi.nlm.nih.gov/30830587/) (https://beta.clinicaltrials.gov/study/NCT04881201). GDAP1-related CMT is an unusually severe form of CMT and one of the most common autosomal recessive forms with several therapeutic developments in process, (https://pubmed.ncbi.nlm.nih.gov/34274972/),(https://pubmed.ncbi.nlm.nih.gov/34440148/). SORD-related CMT is estimated to affect more than 60,000 persons worldwide, likely the most common autosomal recessive form of CMT, with active enrollment in a phase III clinical trial (https://clinicaltrials.gov/ct2/show/NCT05397665). Furthermore, the increasing number of variants of unknown significance associated with SORD will require expedited resolution to enable therapeutic engagement in the active clinical trials.