Inherited neuropathies are clinically and genetically heterogeneous. At least 28 
genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT) 
and related inherited neuropathies. Most causes of inherited neuropathy have 
been discovered by positional cloning technique and in the past two years, the 
pace of CMT gene discovery has accelerated. Genetic studies have revealed the 
following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, 
EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating 
form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal 
recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for 
CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for 
AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 
for CMT-DI (autosomal dominant CMT with intermediate nerve conduction 
velocities); and DHH for minifascicular neuropathy. These discovered CMT causing 
genes/proteins include those which show unpredictable correlations with the 
peripheral nervous system. However, these genes/proteins are definitely 
important for the peripheral nerve, and their discovery should pave the way for 
dramatic progress in the understanding of peripheral nerve biology. On the other 
hand, genotype-phenotype correlations of these genes are also important in order 
to understand the pathomechanisms of inherited neuropathy. Because, based on 
mutation studies, a large number of genes associated with both the CMT1/4 and 
CMT2 forms have been identified, it is usually difficult to predict the 
causative gene based on clinical information from patients without specific 
complications. To clarify the specific features and molecular mechanisms of five 
diseases that we previously reported, we reviewed recent progress in HMSN-P 
linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 
caused by SBF2/MTMR13, and SCAN1 caused by TDP1. HMSN-P is characterized by late 
onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp 
and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin 
are associated with a broad spectrum of demyelinating neuropathies including 
DSS, a sensory dominant form and early onset slowly progressive CMT. 
Pathologically, loss of myelinated fibers, demyelination, small onion bulb 
formations, tomacula formation and myelin foldings were seen in sural nerves. 
Absence of septate like junction in the paranodal loop suggests that periaxin 
could be required for the adhesion complex. GDAP1 is a relatively common cause 
of CMT4. Half of reported patients showed the demyelinating form, while the rest 
showed the axonal form. The typical feature of CMT4A is paresis of the vocal 
cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile 
onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations 
cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. 
SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 
3-phosphoinositide signaling pathway. Clinical phenotypes of patients with TDP1, 
APTX, or SETX mutations share common clinical findings, namely cerebellar ataxia 
and axonal neuropathy. TDP1 and aprataxin both act on the single strand break 
repair pathway, with TDP1 working specifically on topoisomerase I related SSBR. 
Senataxin is a RNA helicase acting on RNA maturation and termination in yeast. 
Since these three proteins share a common pathway, disruption in any of them 
could induce a delay in the transcription process. The low rate of protein 
supply could lead to deaths of large neuronal cells.