Surprisingly, Rab18 colocalizes, cofractionates, and coprecipitates with the lysosomal regulator Rab7, mutations of which cause Charcot-Marie-Tooth (CMT) neuropathy type 2B.
Since peripherin plays a role not only in neurite outgrowth during development but also in axonal regeneration after injury, these data suggest that the altered interaction between disease-causing RAB7A mutants and peripherin could play an important role in CMT2Bneuropathy.
Despite a growing body of evidence concerning the gene structures responsible for genetically heterogenous CMT2B and other CMT2 neuropathies, little is known about the in vitro neuropathy model and how CMT2B-associated mutation-caused aberrant neuritogenesis is properly reversed.
Consistently, mutations or dysfunctions of Rab7 result in traffic disorders, which cause various diseases, such as neuropathy, cancer and lipid metabolism disease.
In particular, CMT type 2B (CMT2B) neuropathies are characterized by severe sensory loss, often complicated by infections, arthropathy, and amputations.
Because motor symptoms were prominent in these latter two kinships, the disease was designated HMSN type IIB or Charcot-Marie-Tooth type 2B (CMT2B) neuropathy.
Three congenital disorders have been localised to this region: blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), Charcot-Marie-Tooth neuropathy type IIB (CMT2B) and Mobius syndrome type 2 (MBS2).